Enhanced tumor-forming capacity for immortalized melanocytes expressing melanoma growth stimulatory activity/growth-regulated cytokine beta and gamma proteins.

Owen JD, Strieter R, Burdick M, Haghnegahdar H, Nanney L, Shattuck-Brandt R, Richmond A
Int J Cancer. 1997 73 (1): 94-103

PMID: 9334815 · DOI:10.1002/(sici)1097-0215(19970926)73:1<94::aid-ijc15>3.0.co;2-5

Three human MGSA/GRO genes encode 3 highly related chemokines, MGSA/GRO alpha, -beta and -gamma. All 3 MGSA/GRO proteins bind to the same receptors, but with differing affinities, and stimulate a number of biological responses including chemotaxis, angiogenesis, and growth regulation. We have previously demonstrated that MGSA/GRO alpha can be isolated from culture medium conditioned by malignant melanoma cells and that continuous secretion of MGSA/GRO alpha contributes to the transformation of immortalized murine melanocytes. The present study was designed to determine whether MGSA/GRO beta or -gamma have similar effects on melanocyte tumorigenicity. Stable Melan-a clones expressing either human MGSA/GRO beta or -gamma exhibited enhanced ability to form large colonies in soft agar and tumors in nude mice. The clones expressing the MGSA/GRO beta or -gamma transgene formed tumors within 2 months after injection; the tumors were highly pigmented and expressed immunoreactive MGSA/GRO beta or -gamma protein. Furthermore, when conditioned medium from Melan-a clones expressing MGSA/GRO alpha, -beta or -gamma transgenes were examined for the ability to induce angiogenesis in the rat cornea, strong angiogenic responses were observed. This angiogenic response was blocked by antibodies to the respective MGSA/GRO protein, but not by normal rabbit serum. By contrast, angiogenic responses were observed in only 2 of 12 corneal implants (17%) containing medium conditioned by Melan-a clones expressing the neomycin resistance marker alone.

MeSH Terms (22)

Amino Acid Sequence Animals Chemokine CXCL1 Chemokines Chemokines, CXC Chemotactic Factors Growth Substances Humans Intercellular Signaling Peptides and Proteins Interleukin-8 Melanoma Mice Mice, Nude Molecular Sequence Data Neovascularization, Pathologic Rabbits Rats Rats, Inbred F344 Receptors, Interleukin Receptors, Interleukin-8B Transgenes Tumor Cells, Cultured

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