In various literature reports, CXCR4 interacting with CXCL12 has been said to cause metastasis in breast and prostate cancers. In colorectal cancers, reports have stated that the cancer cells respond to CCL20, meaning they contain the CCR6 receptor. However, shouldn't these three cancer cell lines all have the same receptors, since they are all epithelial in origin?
Hello Roy, Here are some thoughts.
Very briefly:
One of the reasons could be the estrogen signaling in breast cancer cells that upregulates the expression of CXCL12 and its receptor directly or indirectly. Similarly, in prostate cancer, the hormonal signaling may be involved. There is no such signaling in colorectal cancer cell lines, which might partially explain the difference even though all three cell lines are of epithelial origin.
CXCR4 presence in tumor cells might explain why a tumor gets stromal involvement in vivo.
Hello Roy,
Well, recent reports have indicated that CXCR4 and CXCL12 axis also play important role in the metastasis of colorectal cancer (CRC) cells. CXCR4 expression has found to be high in CRC cells, though CXCL12 expression is very less (according to most of the published reports). However, cancer associated fibroblasts do have high expression for the CXCL12 ligand, suggesting inverse association between CXCR4 expression tumor cells and CXCL12 expressing fibroblasts cells. Moreover, liver has high expression for CXCL12, which possibly explains why it is the primary site for CRC metastasis. Not only liver, lung, adrenal glands and bone marrow also have high expression for CXCL12 under normal condition, which further make them a suitable choice for homing for CXCR4 bearing CRC cells.
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