Tumor cells CXCR4 expressed

Thus, expression of CXCR4 on tumor cells, which is common to many breast cancers as well as other cancer types, may contribute to malignant behavior in several ways. CXCR4 expression by tumor cells may interact with CXCL12 to facilitate tumor cell growth and escape from oxygen starvation-induced apoptosis and as a mechanism to home (metastasize) to secondary sites. 

Marchesi F, Monti P, Leone BE, et al. Increased survival, proliferation, and migration in metastatic human pancreatic tumor cells expressing functional CXCR4. Cancer Res 2004 64 8420-8427. 

The bottom line is that CXCR4 is expressed in the normal stem cells of different organs/tissues. This may help to explain why some tumors express CXCR4, and why we believe these malignant cells may derive from CXCR4 expressing normal stem cells (Table 2). 

Table 2 Examples of tumors expressing CXCR4 that may derive from the normal stem cells which express CXCR4 (Adapted From Ref 9)...

The SDF-1-CXCR4 axis may influence the biology of tumors, ft is believed that the organs that express high SDF-1 (e.g., lymph nodes, lungs, liver, or bones) may direct the metastasis of CXCR4-expressing tumor cells. 

Kaifi J. T., Yekebas E. F., Schurr P., et al. (2005) Tumor-cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer. J Natl Cancer Inst 97,1840-7. 

Retz M, Sidhu S, Blaveri E, et al. (2005) CXCR4 expression reflects tumor progression and regulates motility of bladder cancer cells. Int J Cancer 114 182-189... 

Endothelins and their receptors may be induced within the tumor microenvironment by hypoxia via stabilization of HIF-la as well as by inflammatory cytokines and chemokines [44]. These studies imply that multiple factors within the tumor microenvironment upregulate endothelin expression in local tumor regions, which in turn induces CCR7 expression by tumor cells. Interestingly, another chemokine receptor (i.e., CXCR4) associated with cancer cells is also induced by hypoxia via HIF-1-dependent mechanisms [19], suggesting that hypoxia may be an inducer of a variety of chemokine receptors. (See Chapter 3.)... 

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