Enhanced tumor-forming capacity for immortalized melanocytes expressing melanoma growth stimulatory activity/growth-regulated cytokine beta and gamma proteins.
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.
Owen
J D
JD
Department of Veterans Affairs, Nashville, TN, USA.
Strieter
R
R
Burdick
M
M
Haghnegahdar
H
H
Nanney
L
L
Shattuck-Brandt
R
R
Richmond
A
A
D000595:Amino Acid Sequence; D000818:Animals; D054360:Chemokine CXCL1; D018925:Chemokines / Q000502:physiology*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006133:Growth Substances / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000502:physiology; D008545:Melanoma / Q000209:etiology / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D018123:Receptors, Interleukin / Q000032:analysis / Q000235:genetics; D023063:Receptors, Interleukin-8B; D019076:Transgenes; D014407:Tumor Cells, Cultured
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; C513297:Cxcl1 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D018123:Receptors, Interleukin; D023063:Receptors, Interleukin-8B