The
chemokines and their receptors are a superfamily of small secreted molecules that control the migration of many cell types in the body. Several years ago it became clear that some
chemokines and receptors regulate the migration of certain cells in the lymphoid system, and this raised the possibility that
chemokines could also control the migration of
tumor cells in the body.
Breast cancer cells were found to express
chemokine receptors in a nonrandom manner, and these observations pointed to several
chemokine/receptor pairs that control
tumor-cell migration. The most important
ligand/receptors pairs in these phenomena include CXCL12/CXCR4 and CCL21/CCR7. Since then, there has been intense interest in this area and many studies have been published, especially on CXCR4. These studies point to the following conclusions: (i)
Tumors express
chemokine receptors in a nonrandom manner. (ii) CXCR4 is the most widely expressed
chemokine receptor in many different
cancers. (iii) CCR7 is also expressed by many
cancers, and is likely to mediate
metastasis to the lymph nodes in selected
cancers. (iv) The effects of CXCL12 on CXCR4-bearing
tumor cells likely include many other functions (growth, differentiation) besides migration. During normal development, the interaction CXCL12/CXCR4 is known to be involved in organogenesis. This process shares many characteristics with
metastasis, and represents one of the key areas of future research.