Enhanced tumor-forming capacity for immortalized melanocytes expressing melanoma growth stimulatory activity/growth-regulated cytokine β and γ proteins
✍ Scribed by James D. Owen; Robert Strieter; Marie Burdick; Hamid Haghnegahdar; Lillian Nanney; Rebecca Shattuck-Brandt; Ann Richmond
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- French
- Weight
- 234 KB
- Volume
- 73
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Three human MGSA/GRO genes encode 3 highly related chemokines, MGSA/GRO␣, - and -␥. 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␣ can be isolated from culture medium conditioned by malignant melanoma cells and that continuous secretion of MGSA/ GRO␣ contributes to the transformation of immortalized murine melanocytes. The present study was designed to determine whether MGSA/GRO or -␥ have similar effects on melanocyte tumorigenicity. Stable Melan-a clones expressing either human MGSA/GRO or -␥ exhibited enhanced ability to form large colonies in soft agar and tumors in nude mice. The clones expressing the MGSA/GRO or -␥ transgene formed tumors within 2 months after injection; the tumors were highly pigmented and expressed immunoreactive MGSA/GRO or -␥ protein. Furthermore, when conditioned medium from Melan-a clones expressing MGSA/ GRO␣, - or -␥ 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. Int.