Enhanced tumor-forming capacity for immortalized melanocytes expressing melanoma growth stimulatory activity/growth-regulated cytokine β and γ proteins

作者：James D. Owen, Robert M. Strieter, Marie D. Burdick, Hamid Haghnegahdar, Lillian B. Nanney, Rebecca L. Shattuck-Brandt, Ann J. Richmond · 发表于：International Journal of Cancer · 年份：1997 · DOI：10.1002/(sici)1097-0215(19970926)73:1<94::aid-ijc15>3.0.co;2-5 · 被引用次数：133 · 研究领域：Chemokine receptors and signaling、Cell Adhesion Molecules Research、Angiogenesis and VEGF in Cancer

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 e...