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Differential beta‐3 integrin of CXCR3, CXCR4, and CXCR7 clustering on breast cancer cells in response to CXCL11, CXCL12, and Adrenomedullin
Author(s) -
Mosley LaSharon Denise,
Sharma Praveen K,
Singh Rajesh,
Singh Shailesh,
Lillard James W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.665.8
Subject(s) - cancer research , cxcr3 , chemokine receptor , cxcr4 , metastasis , adrenomedullin , breast cancer , chemokine , cxcl11 , integrin , biology , chemotaxis , cancer , medicine , receptor , immunology
Metastasis is responsible for essentially all breast cancer (BrCa) related deaths; therefore, therapies designed to prevent the spread of BrCa cells are greatly needed. Similarly, the anti‐apoptotic mechanisms employed by BrCa cells to survive in serum‐free environments and apoptosis‐inducing therapeutics are numerous and contribute significantly to the morbidity and mortality of this disease. Chemokines have been demonstrated to support BrCa metastasis and may also activate anti‐apopototic mechanisms. In this regard, BrCa cells express functionally active CXCR3, CXCR4, and CXCR7 to presumably support adhesion, invasion, and cell survival. The ligands for CXCR7 are CXCL11 (also binds CXCR3), CXCL12 (also binds CXCR4), calcitonin‐related gene peptide (CRGP), and adrenomedullin (AM). We provide evidence that CXCR7 expression correlates with breast tumor staging and confirm that this receptor; along with CXCR3 and CXCR4, are expressed by BrCa cell lines. We also show that CXCL11, CXCL12, and AM, but not CRGP, differentially modulates β 3 integrin clustering and CXCR3, CXCR4, and CXCR7 aggregation in BrCa cell lines. Chemokine receptor aggregation coupled to integrin clustering induces signals to support cell survival and adhesion. Taken together these studies provide important and novel information regarding the cellular and molecular mechanisms of CXCR3, CXCR4 and CXCR7 in breast tumor progression.