The tumorigenic and angiogenic effects of MGSA/GRO proteins in melanoma

Hamid Haghnegahdar, Jianguo Du, Ding Zhi Wang, Robert M. Strieter, Marie D. Burdick, Lillian B. Nanney, Nancy Cardwell, Jing Luan, Rebecca Shattuck-Brandt, Ann Richmond

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

Continuous expression of the MGSA/GROα, β, or γ chemokine bestows tumor-forming capacity to the immortalized murine melanocyte cell line, melan-a. The mechanism for this transformation is unclear, although both autocrine and paracrine processes are possible because melan-a cells as well as endothelial cells express a low level of the receptor for this ligand. To further define the role of MGSA/GRO proteins in melanocyte transformation, two types of experiments were designed to neutralize the biological effects of MGSA/GRO in the transfected melan-a clones: (1) the effect of neutralizing antiserum to MGSA/GRO proteins on melan-a tumor growth was assessed; (2) the tumor-forming capacity of melan-a clones expressing ELR motif-mutated forms of MGSA/GRO with compromised receptor affinity was compared to the tumor- forming capacity of clones expressing wild-type MGSA/GRO. These experiments revealed that SCID mice inoculated with MGSA/GROα- or γ-expressing melan-a cells and subsequently treated with antiserum to the respective chemokine exhibited decreased tumor growth. This reduction in tumor growth was accompanied by declining angiogenic activity in MGSA/GROγ-expressing tumors. Moreover, athymic nude mice injected with melan-a cells expressing ELR-mutant forms of MGSA/GROα exhibited markedly impaired tumor-forming capacity compared with those mice injected with melan-a clones expressing wild-type MGSA/GRO. These data suggest that continuous expression of MGSA/GRO proteins may facilitate tumor growth by stimulating the growth of microvessels into the tumor (paracrine) and by affecting melanocyte growth (autocrine).

Original languageEnglish (US)
Pages (from-to)53-62
Number of pages10
JournalJournal of Leukocyte Biology
Volume67
Issue number1
DOIs
StatePublished - 2000

Keywords

  • Angiogenesis
  • Chemokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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