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

Int J Cancer. 1997 Sep 26;73(1):94-103. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


  • CXCL1 protein, human
  • Chemokine CXCL1
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Cxcl1 protein, mouse
  • Cxcl1 protein, rat
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • Receptors, Interleukin
  • Receptors, Interleukin-8B