Expression of functional chemokine receptors CXCR3 and CXCR4 on human melanoma cells

Chemokines are secreted into the tumor microenvironment by tumor-infiltrati ng inflammatory cells as well as by tumor cells. Chemokine receptors mediat e agonist-dependent cell responses, including migration and activation of s everal signaling pathways. In the present study we show that several human melanoma cell lines and melanoma cells on macroscopically infiltrated lymph nodes express the chemokine receptors CXCR3 and CXCR4. Using the highly in vasive melanoma cell line BLM, we demonstrate that the chemokine Mig, a lig and for CXCR3, activates the small GTPases RhoA and Rac1, induces a reorgan ization of the actin cytoskeleton, and triggers cell chemotaxis and modulat ion of integrin VIA-5- and VIA-4-dependent cell adhesion to fibronectin. Fu rthermore, the chemokine SDF-1 alpha, the ligand of CXCR4, triggered modula tion of beta (1) integrin-dependent melanoma cell adhesion to fibronectin. Additionally, Mig and SDF-1 alpha activated MAPKs p44/42 and p38 on melanom a cells. Expression of functional CXCR3 and CXCR4 receptors on melanoma cel ls indicates that they might contribute to cell motility during invasion as well as to regulation of cell proliferation and survival.