التفاصيل البيبلوغرافية
| العنوان: |
A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis. |
| المؤلفون: |
Acharyya, Swarnali1, Oskarsson, Thordur1, Vanharanta, Sakari1, Malladi, Srinivas1, Kim, Juliet1, Morris, Patrick G.2, Manova-Todorova, Katia3, Leversha, Margaret4, Hogg, Nancy5, Seshan, Venkatraman E.6, Norton, Larry2, Brogi, Edi7, Massagué, Joan1,8 massaguj@mskcc.org |
| المصدر: |
Cell. Jul2012, Vol. 150 Issue 1, p165-178. 14p. |
| مصطلحات موضوعية: |
*CHEMOKINES, *PARACRINE mechanisms, *METASTASIS, *CARCINOMA, *ENDOTHELIAL cells, *BREAST cancer, *TUMOR necrosis factors |
| مستخلص: |
Summary Metastasis and chemoresistance in cancer are linked phenomena, but the molecular basis for this link is unknown. We uncovered a network of paracrine signals between carcinoma, myeloid, and endothelial cells that drives both processes in breast cancer. Cancer cells that overexpress CXCL1 and 2 by transcriptional hyperactivation or 4q21 amplification are primed for survival in metastatic sites. CXCL1/2 attract CD11b + Gr1 + myeloid cells into the tumor, which produce chemokines including S100A8/9 that enhance cancer cell survival. Although chemotherapeutic agents kill cancer cells, these treatments trigger a parallel stromal reaction leading to TNF-α production by endothelial and other stromal cells. TNF-α via NF-kB heightens the CXCL1/2 expression in cancer cells, thus amplifying the CXCL1/2-S100A8/9 loop and causing chemoresistance. CXCR2 blockers break this cycle, augmenting the efficacy of chemotherapy against breast tumors and particularly against metastasis. This network of endothelial-carcinoma-myeloid signaling interactions provides a mechanism linking chemoresistance and metastasis, with opportunities for intervention. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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