CXCR4 CXCR7 effects in melanoma & melanocytes v1

Chemokines are small signaling proteins released by cells in response to chemical stimuli in their environment. The chemokine stromal cell-derived factor-1 (SDF1/CXCL12) plays a role in the growth and metastasis of multiple cancers, including melanoma. SDF1/CXCL12 has two known receptors: CXCR4 and CXCR7. CXCR4 receptor signaling influences many cell responses, including the migration of neural crest cells and the amount of receptor expression upregulation in melanoma. CXCR7 receptor signaling influences melanocyte migration and constrains melanoma tumor growth in vivo, while CXCR4 receptor signaling does not. It is not known, however, if CXCR7 directly affects melanocyte and melanoma cell migration. Here, CXCR4 and CXCR7 receptor signaling were directly studied in vitro in human primary melanocytes and mouse B16-F10 melanoma cell line for migration when both receptors, individually and in combination, were genetically silenced. The silencing of CXCR7 clearly resulted in statistically significant inhibition of migration of both melanocytes and B16-F10 melanoma cells while the effects of CXCR4 silencing of migration inhibition was less clear. These results suggest that the CXCR7 receptor is more relevant than the CXCR4 receptor for the migratory capabilities of melanocytes and B16-F10 melanoma cells. These findings support down regulation or inhibition of the CXCR7 receptor through targeted therapies may be beneficial in melanoma treatment.