The tumorigenic and angiogenic effects of MGSA/GRO proteins in melanoma.

Haghnegahdar H, Du J, Wang D, Strieter RM, Burdick MD, Nanney LB, Cardwell N, Luan J, Shattuck-Brandt R, Richmond A
J Leukoc Biol. 2000 67 (1): 53-62

PMID: 10647998 · PMCID: PMC2669312 · DOI:10.1002/jlb.67.1.53

Continuous expression of the MGSA/GROalpha, beta, or gamma chemokine bestows tumor-forming capacity to the immortalized murine melanocyte cell line, melan-a. The mechanism for this transformation is unclear, although both autocrine and paracrine processes are possible because melan-a cells as well as endothelial cells express a low level of the receptor for this ligand. To further define the role of MGSA/GRO proteins in melanocyte transformation, two types of experiments were designed to neutralize the biological effects of MGSA/GRO in the transfected melan-a clones: (1) the effect of neutralizing antiserum to MGSA/GRO proteins on melan-a tumor growth was assessed; (2) the tumor-forming capacity of melan-a clones expressing ELR motif-mutated forms of MGSA/GRO with compromised receptor affinity was compared to the tumor-forming capacity of clones expressing wild-type MGSA/GRO. These experiments revealed that SCID mice inoculated with MGSA/GROalpha- or gamma-expressing melan-a cells and subsequently treated with antiserum to the respective chemokine exhibited decreased tumor growth. This reduction in tumor growth was accompanied by declining angiogenic activity in MGSA/GROgamma-expressing tumors. Moreover, athymic nude mice injected with melan-a cells expressing ELR-mutant forms of MGSA/GROalpha exhibited markedly impaired tumor-forming capacity compared with those mice injected with melan-a clones expressing wild-type MGSA/GRO. These data suggest that continuous expression of MGSA/GRO proteins may facilitate tumor growth by stimulating the growth of microvessels into the tumor (paracrine) and by affecting melanocyte growth (autocrine).

MeSH Terms (14)

Animals Cell Transformation, Neoplastic Chemokine CXCL1 Chemokines, CXC Chemotactic Factors Female Gene Expression Regulation, Neoplastic Growth Substances Intercellular Signaling Peptides and Proteins Melanoma, Experimental Mice Mice, Nude Neoplasm Proteins Neovascularization, Pathologic

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