Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer
Abstract Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened dis...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Tuomela, Johanna [verfasserIn] Sandholm, Jouko [verfasserIn] Karihtala, Peeter [verfasserIn] Ilvesaro, Joanna [verfasserIn] Vuopala, Katri S. [verfasserIn] Kauppila, Joonas H. [verfasserIn] Kauppila, Saila [verfasserIn] Chen, Dongquan [verfasserIn] Pressey, Christine [verfasserIn] Härkönen, Pirkko [verfasserIn] Harris, Kevin W. [verfasserIn] Graves, David [verfasserIn] Auvinen, Päivi K. [verfasserIn] Soini, Ylermi [verfasserIn] Jukkola-Vuorinen, Arja [verfasserIn] Selander, Katri S. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2012 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Breast cancer research and treatment - Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981, 135(2012), 2 vom: 31. Juli, Seite 481-493 |
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| Übergeordnetes Werk: |
volume:135 ; year:2012 ; number:2 ; day:31 ; month:07 ; pages:481-493 |
| Links: |
|---|
| DOI / URN: |
10.1007/s10549-012-2181-7 |
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| Katalog-ID: |
SPR011087382 |
|---|
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| 520 | |a Abstract Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened disease-specific survival in patients with triple negative but not with ER+ breast cancers. A likely mechanism of this clinical finding involves differential responses to hypoxia. Our pre-clinical studies indicate that while TLR9 expression is hypoxia-regulated, low TLR9 expression has different effects on triple negative and ER+ breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9 siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly due to differential TLR9-regulated TIMP-3 expression, which remains detectable in ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our results demonstrate a novel role for this innate immunity receptor in cancer biology and suggest that TLR9 expression may be a novel marker for triple-negative breast cancer patients who are at a high risk of relapse. Furthermore, these results suggest that interventions or events, which induce hypoxia or down-regulate TLR9 expression in triple-negative breast cancer cells may actually induce their spread. | ||
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| 650 | 4 | |a Triple negative |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Hypoxia |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Invasion |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Breast cancer |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Sandholm, Jouko |e verfasserin |4 aut | |
| 700 | 1 | |a Karihtala, Peeter |e verfasserin |4 aut | |
| 700 | 1 | |a Ilvesaro, Joanna |e verfasserin |4 aut | |
| 700 | 1 | |a Vuopala, Katri S. |e verfasserin |4 aut | |
| 700 | 1 | |a Kauppila, Joonas H. |e verfasserin |4 aut | |
| 700 | 1 | |a Kauppila, Saila |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Dongquan |e verfasserin |4 aut | |
| 700 | 1 | |a Pressey, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Härkönen, Pirkko |e verfasserin |4 aut | |
| 700 | 1 | |a Harris, Kevin W. |e verfasserin |4 aut | |
| 700 | 1 | |a Graves, David |e verfasserin |4 aut | |
| 700 | 1 | |a Auvinen, Päivi K. |e verfasserin |4 aut | |
| 700 | 1 | |a Soini, Ylermi |e verfasserin |4 aut | |
| 700 | 1 | |a Jukkola-Vuorinen, Arja |e verfasserin |4 aut | |
| 700 | 1 | |a Selander, Katri S. |e verfasserin |4 aut | |
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10.1007/s10549-012-2181-7 doi (DE-627)SPR011087382 (SPR)s10549-012-2181-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.92 bkl Tuomela, Johanna verfasserin aut Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened disease-specific survival in patients with triple negative but not with ER+ breast cancers. A likely mechanism of this clinical finding involves differential responses to hypoxia. Our pre-clinical studies indicate that while TLR9 expression is hypoxia-regulated, low TLR9 expression has different effects on triple negative and ER+ breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9 siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly due to differential TLR9-regulated TIMP-3 expression, which remains detectable in ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our results demonstrate a novel role for this innate immunity receptor in cancer biology and suggest that TLR9 expression may be a novel marker for triple-negative breast cancer patients who are at a high risk of relapse. Furthermore, these results suggest that interventions or events, which induce hypoxia or down-regulate TLR9 expression in triple-negative breast cancer cells may actually induce their spread. Toll-like receptor-9 (dpeaa)DE-He213 Triple negative (dpeaa)DE-He213 Hypoxia (dpeaa)DE-He213 Invasion (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Sandholm, Jouko verfasserin aut Karihtala, Peeter verfasserin aut Ilvesaro, Joanna verfasserin aut Vuopala, Katri S. verfasserin aut Kauppila, Joonas H. verfasserin aut Kauppila, Saila verfasserin aut Chen, Dongquan verfasserin aut Pressey, Christine verfasserin aut Härkönen, Pirkko verfasserin aut Harris, Kevin W. verfasserin aut Graves, David verfasserin aut Auvinen, Päivi K. verfasserin aut Soini, Ylermi verfasserin aut Jukkola-Vuorinen, Arja verfasserin aut Selander, Katri S. verfasserin aut Enthalten in Breast cancer research and treatment Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981 135(2012), 2 vom: 31. Juli, Seite 481-493 (DE-627)320433722 (DE-600)2004077-5 1573-7217 nnns volume:135 year:2012 number:2 day:31 month:07 pages:481-493 https://dx.doi.org/10.1007/s10549-012-2181-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.92 ASE AR 135 2012 2 31 07 481-493 |
| spelling |
10.1007/s10549-012-2181-7 doi (DE-627)SPR011087382 (SPR)s10549-012-2181-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.92 bkl Tuomela, Johanna verfasserin aut Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened disease-specific survival in patients with triple negative but not with ER+ breast cancers. A likely mechanism of this clinical finding involves differential responses to hypoxia. Our pre-clinical studies indicate that while TLR9 expression is hypoxia-regulated, low TLR9 expression has different effects on triple negative and ER+ breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9 siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly due to differential TLR9-regulated TIMP-3 expression, which remains detectable in ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our results demonstrate a novel role for this innate immunity receptor in cancer biology and suggest that TLR9 expression may be a novel marker for triple-negative breast cancer patients who are at a high risk of relapse. Furthermore, these results suggest that interventions or events, which induce hypoxia or down-regulate TLR9 expression in triple-negative breast cancer cells may actually induce their spread. Toll-like receptor-9 (dpeaa)DE-He213 Triple negative (dpeaa)DE-He213 Hypoxia (dpeaa)DE-He213 Invasion (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Sandholm, Jouko verfasserin aut Karihtala, Peeter verfasserin aut Ilvesaro, Joanna verfasserin aut Vuopala, Katri S. verfasserin aut Kauppila, Joonas H. verfasserin aut Kauppila, Saila verfasserin aut Chen, Dongquan verfasserin aut Pressey, Christine verfasserin aut Härkönen, Pirkko verfasserin aut Harris, Kevin W. verfasserin aut Graves, David verfasserin aut Auvinen, Päivi K. verfasserin aut Soini, Ylermi verfasserin aut Jukkola-Vuorinen, Arja verfasserin aut Selander, Katri S. verfasserin aut Enthalten in Breast cancer research and treatment Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981 135(2012), 2 vom: 31. Juli, Seite 481-493 (DE-627)320433722 (DE-600)2004077-5 1573-7217 nnns volume:135 year:2012 number:2 day:31 month:07 pages:481-493 https://dx.doi.org/10.1007/s10549-012-2181-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.92 ASE AR 135 2012 2 31 07 481-493 |
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10.1007/s10549-012-2181-7 doi (DE-627)SPR011087382 (SPR)s10549-012-2181-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.92 bkl Tuomela, Johanna verfasserin aut Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened disease-specific survival in patients with triple negative but not with ER+ breast cancers. A likely mechanism of this clinical finding involves differential responses to hypoxia. Our pre-clinical studies indicate that while TLR9 expression is hypoxia-regulated, low TLR9 expression has different effects on triple negative and ER+ breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9 siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly due to differential TLR9-regulated TIMP-3 expression, which remains detectable in ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our results demonstrate a novel role for this innate immunity receptor in cancer biology and suggest that TLR9 expression may be a novel marker for triple-negative breast cancer patients who are at a high risk of relapse. Furthermore, these results suggest that interventions or events, which induce hypoxia or down-regulate TLR9 expression in triple-negative breast cancer cells may actually induce their spread. Toll-like receptor-9 (dpeaa)DE-He213 Triple negative (dpeaa)DE-He213 Hypoxia (dpeaa)DE-He213 Invasion (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Sandholm, Jouko verfasserin aut Karihtala, Peeter verfasserin aut Ilvesaro, Joanna verfasserin aut Vuopala, Katri S. verfasserin aut Kauppila, Joonas H. verfasserin aut Kauppila, Saila verfasserin aut Chen, Dongquan verfasserin aut Pressey, Christine verfasserin aut Härkönen, Pirkko verfasserin aut Harris, Kevin W. verfasserin aut Graves, David verfasserin aut Auvinen, Päivi K. verfasserin aut Soini, Ylermi verfasserin aut Jukkola-Vuorinen, Arja verfasserin aut Selander, Katri S. verfasserin aut Enthalten in Breast cancer research and treatment Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981 135(2012), 2 vom: 31. Juli, Seite 481-493 (DE-627)320433722 (DE-600)2004077-5 1573-7217 nnns volume:135 year:2012 number:2 day:31 month:07 pages:481-493 https://dx.doi.org/10.1007/s10549-012-2181-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.92 ASE AR 135 2012 2 31 07 481-493 |
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10.1007/s10549-012-2181-7 doi (DE-627)SPR011087382 (SPR)s10549-012-2181-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.92 bkl Tuomela, Johanna verfasserin aut Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened disease-specific survival in patients with triple negative but not with ER+ breast cancers. A likely mechanism of this clinical finding involves differential responses to hypoxia. Our pre-clinical studies indicate that while TLR9 expression is hypoxia-regulated, low TLR9 expression has different effects on triple negative and ER+ breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9 siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly due to differential TLR9-regulated TIMP-3 expression, which remains detectable in ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our results demonstrate a novel role for this innate immunity receptor in cancer biology and suggest that TLR9 expression may be a novel marker for triple-negative breast cancer patients who are at a high risk of relapse. Furthermore, these results suggest that interventions or events, which induce hypoxia or down-regulate TLR9 expression in triple-negative breast cancer cells may actually induce their spread. Toll-like receptor-9 (dpeaa)DE-He213 Triple negative (dpeaa)DE-He213 Hypoxia (dpeaa)DE-He213 Invasion (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Sandholm, Jouko verfasserin aut Karihtala, Peeter verfasserin aut Ilvesaro, Joanna verfasserin aut Vuopala, Katri S. verfasserin aut Kauppila, Joonas H. verfasserin aut Kauppila, Saila verfasserin aut Chen, Dongquan verfasserin aut Pressey, Christine verfasserin aut Härkönen, Pirkko verfasserin aut Harris, Kevin W. verfasserin aut Graves, David verfasserin aut Auvinen, Päivi K. verfasserin aut Soini, Ylermi verfasserin aut Jukkola-Vuorinen, Arja verfasserin aut Selander, Katri S. verfasserin aut Enthalten in Breast cancer research and treatment Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981 135(2012), 2 vom: 31. Juli, Seite 481-493 (DE-627)320433722 (DE-600)2004077-5 1573-7217 nnns volume:135 year:2012 number:2 day:31 month:07 pages:481-493 https://dx.doi.org/10.1007/s10549-012-2181-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.92 ASE AR 135 2012 2 31 07 481-493 |
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10.1007/s10549-012-2181-7 doi (DE-627)SPR011087382 (SPR)s10549-012-2181-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.92 bkl Tuomela, Johanna verfasserin aut Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened disease-specific survival in patients with triple negative but not with ER+ breast cancers. A likely mechanism of this clinical finding involves differential responses to hypoxia. Our pre-clinical studies indicate that while TLR9 expression is hypoxia-regulated, low TLR9 expression has different effects on triple negative and ER+ breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9 siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly due to differential TLR9-regulated TIMP-3 expression, which remains detectable in ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our results demonstrate a novel role for this innate immunity receptor in cancer biology and suggest that TLR9 expression may be a novel marker for triple-negative breast cancer patients who are at a high risk of relapse. Furthermore, these results suggest that interventions or events, which induce hypoxia or down-regulate TLR9 expression in triple-negative breast cancer cells may actually induce their spread. Toll-like receptor-9 (dpeaa)DE-He213 Triple negative (dpeaa)DE-He213 Hypoxia (dpeaa)DE-He213 Invasion (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Sandholm, Jouko verfasserin aut Karihtala, Peeter verfasserin aut Ilvesaro, Joanna verfasserin aut Vuopala, Katri S. verfasserin aut Kauppila, Joonas H. verfasserin aut Kauppila, Saila verfasserin aut Chen, Dongquan verfasserin aut Pressey, Christine verfasserin aut Härkönen, Pirkko verfasserin aut Harris, Kevin W. verfasserin aut Graves, David verfasserin aut Auvinen, Päivi K. verfasserin aut Soini, Ylermi verfasserin aut Jukkola-Vuorinen, Arja verfasserin aut Selander, Katri S. verfasserin aut Enthalten in Breast cancer research and treatment Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981 135(2012), 2 vom: 31. Juli, Seite 481-493 (DE-627)320433722 (DE-600)2004077-5 1573-7217 nnns volume:135 year:2012 number:2 day:31 month:07 pages:481-493 https://dx.doi.org/10.1007/s10549-012-2181-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.92 ASE AR 135 2012 2 31 07 481-493 |
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Enthalten in Breast cancer research and treatment 135(2012), 2 vom: 31. Juli, Seite 481-493 volume:135 year:2012 number:2 day:31 month:07 pages:481-493 |
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Enthalten in Breast cancer research and treatment 135(2012), 2 vom: 31. Juli, Seite 481-493 volume:135 year:2012 number:2 day:31 month:07 pages:481-493 |
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Toll-like receptor-9 Triple negative Hypoxia Invasion Breast cancer |
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Breast cancer research and treatment |
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Tuomela, Johanna @@aut@@ Sandholm, Jouko @@aut@@ Karihtala, Peeter @@aut@@ Ilvesaro, Joanna @@aut@@ Vuopala, Katri S. @@aut@@ Kauppila, Joonas H. @@aut@@ Kauppila, Saila @@aut@@ Chen, Dongquan @@aut@@ Pressey, Christine @@aut@@ Härkönen, Pirkko @@aut@@ Harris, Kevin W. @@aut@@ Graves, David @@aut@@ Auvinen, Päivi K. @@aut@@ Soini, Ylermi @@aut@@ Jukkola-Vuorinen, Arja @@aut@@ Selander, Katri S. @@aut@@ |
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|
| author |
Tuomela, Johanna |
| spellingShingle |
Tuomela, Johanna ddc 610 bkl 44.92 misc Toll-like receptor-9 misc Triple negative misc Hypoxia misc Invasion misc Breast cancer Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer |
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Tuomela, Johanna |
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@@773@@(DE-627)320433722 |
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electronic Article |
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610 - Medicine & health |
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keep |
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aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
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springer |
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true |
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Not Illustrated |
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1573-7217 |
| topic_title |
610 ASE 44.92 bkl Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer Toll-like receptor-9 (dpeaa)DE-He213 Triple negative (dpeaa)DE-He213 Hypoxia (dpeaa)DE-He213 Invasion (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 |
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ddc 610 bkl 44.92 misc Toll-like receptor-9 misc Triple negative misc Hypoxia misc Invasion misc Breast cancer |
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ddc 610 bkl 44.92 misc Toll-like receptor-9 misc Triple negative misc Hypoxia misc Invasion misc Breast cancer |
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ddc 610 bkl 44.92 misc Toll-like receptor-9 misc Triple negative misc Hypoxia misc Invasion misc Breast cancer |
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Elektronische Aufsätze Aufsätze Elektronische Ressource |
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Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer |
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Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer |
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Tuomela, Johanna |
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Breast cancer research and treatment |
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Tuomela, Johanna Sandholm, Jouko Karihtala, Peeter Ilvesaro, Joanna Vuopala, Katri S. Kauppila, Joonas H. Kauppila, Saila Chen, Dongquan Pressey, Christine Härkönen, Pirkko Harris, Kevin W. Graves, David Auvinen, Päivi K. Soini, Ylermi Jukkola-Vuorinen, Arja Selander, Katri S. |
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10.1007/s10549-012-2181-7 |
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low tlr9 expression defines an aggressive subtype of triple-negative breast cancer |
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Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer |
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Abstract Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened disease-specific survival in patients with triple negative but not with ER+ breast cancers. A likely mechanism of this clinical finding involves differential responses to hypoxia. Our pre-clinical studies indicate that while TLR9 expression is hypoxia-regulated, low TLR9 expression has different effects on triple negative and ER+ breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9 siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly due to differential TLR9-regulated TIMP-3 expression, which remains detectable in ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our results demonstrate a novel role for this innate immunity receptor in cancer biology and suggest that TLR9 expression may be a novel marker for triple-negative breast cancer patients who are at a high risk of relapse. Furthermore, these results suggest that interventions or events, which induce hypoxia or down-regulate TLR9 expression in triple-negative breast cancer cells may actually induce their spread. |
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Abstract Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened disease-specific survival in patients with triple negative but not with ER+ breast cancers. A likely mechanism of this clinical finding involves differential responses to hypoxia. Our pre-clinical studies indicate that while TLR9 expression is hypoxia-regulated, low TLR9 expression has different effects on triple negative and ER+ breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9 siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly due to differential TLR9-regulated TIMP-3 expression, which remains detectable in ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our results demonstrate a novel role for this innate immunity receptor in cancer biology and suggest that TLR9 expression may be a novel marker for triple-negative breast cancer patients who are at a high risk of relapse. Furthermore, these results suggest that interventions or events, which induce hypoxia or down-regulate TLR9 expression in triple-negative breast cancer cells may actually induce their spread. |
| abstract_unstemmed |
Abstract Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened disease-specific survival in patients with triple negative but not with ER+ breast cancers. A likely mechanism of this clinical finding involves differential responses to hypoxia. Our pre-clinical studies indicate that while TLR9 expression is hypoxia-regulated, low TLR9 expression has different effects on triple negative and ER+ breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9 siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly due to differential TLR9-regulated TIMP-3 expression, which remains detectable in ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our results demonstrate a novel role for this innate immunity receptor in cancer biology and suggest that TLR9 expression may be a novel marker for triple-negative breast cancer patients who are at a high risk of relapse. Furthermore, these results suggest that interventions or events, which induce hypoxia or down-regulate TLR9 expression in triple-negative breast cancer cells may actually induce their spread. |
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Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer |
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Sandholm, Jouko Karihtala, Peeter Ilvesaro, Joanna Vuopala, Katri S. Kauppila, Joonas H. Kauppila, Saila Chen, Dongquan Pressey, Christine Härkönen, Pirkko Harris, Kevin W. Graves, David Auvinen, Päivi K. Soini, Ylermi Jukkola-Vuorinen, Arja Selander, Katri S. |
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7.3982754 |