The Role of Chemokines and Receptors in Breast Cancer

HANDEL LAB, UCSD, SKAGGS SCHOOL OF PHARMACY AND PHARMACEUTICAL SCIENCES 

Chemokines/Receptors in Breast Cancer

Rina Salanga and Morgan O'Hayre

In parallel with their role in controlling cell migration during immune responses, chemokines and their receptors have been implicated in the metastatic process by directing the migration of tumor cells to sites of metastasis (see Figure below). The chemokine receptors CXCR4 and CXCR7 are not expressed on normal breast epithelia but they are frequently expressed on breast cancer cells, and there is preferential metastasis of breast cancer cells to sites where their ligand, CXCL12, is constitutively expressed. However, the exact mechanisms of how CXCR4 and CXCR7 enhance metastasis and/or tumor growth and their full implications on disease progression are unknown. Yet it is likely that chemokine receptor signaling may provide more than just a migrational advantage, but also help the metastasized cells establish and survive in secondary environments. Metastasis of primary tumors to secondary organs is the leading cause of death in breast cancer patients. Due to the potential involvement of CXCR4 and CXCR7 in helping metastasized cells grow and survive at metastatic sites, which is believed to be one of the least efficient steps in the metastatic process, these receptors or their downstream targets may represent good therapeutic targets for breast cancer treatment. We are using cell based assays, in vivo experiments and proteomics to study the role of these chemokine receptors in breast cancer.

 

This  figure illustrates many aspects of cancer progression where chemokines/receptors may play a role: growth of the primary tumor, angiogenesis (cell migration of endothelial precursors), metastasis, and growth survival of the metastasized cells which is probably the least efficient step in the metastatic process.  For a review on this subject, click here.The final version of record is available at www.biochemj.org.

Techniques: Proteomics, Tissue Culture, In Vivo Studies, Cell Based Assays