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Enhanced tumor‐forming capacity for immortalized melanocytes expressing melanoma growth stimulatory activity/growth‐regulated cytokine β and γ proteins
Author(s) -
Owen James D.,
Strieter Robert,
Burdick Marie,
Haghnegahdar Hamid,
Nanney Lillian,
ShattuckBrandt Rebecca,
Richmond Ann
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970926)73:1<94::aid-ijc15>3.0.co;2-5
Subject(s) - angiogenesis , biology , cytokine , chemokine , melanocyte , genetically modified mouse , melanoma , transgene , microbiology and biotechnology , cancer research , immunology , immune system , gene , genetics
Three human MGSA/GRO genes encode 3 highly related chemokines, MGSA/GROα, ‐β and ‐γ. 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/GROα can be isolated from culture medium conditioned by malignant melanoma cells and that continuous secretion of MGSA/GROα contributes to the transformation of immortalized murine melanocytes. The present study was designed to determine whether MGSA/GROβ or ‐γ have similar effects on melanocyte tumorigenicity. Stable Melan‐a clones expressing either human MGSA/GROβ or ‐γ exhibited enhanced ability to form large colonies in soft agar and tumors in nude mice. The clones expressing the MGSA/GROβ or ‐γ transgene formed tumors within 2 months after injection; the tumors were highly pigmented and expressed immunoreactive MGSA/GROβ or ‐γ protein. Furthermore, when conditioned medium from Melan‐a clones expressing MGSA/GROα, ‐β or ‐γ 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. J. Cancer 73:94–103, 1997. © 1997 Wiley‐Liss, Inc.