Mutant MCP-1 therapy inhibits tumor angiogenesis and growth of malignant melanoma in mice

Mitsuhisa Koga, Hisashi Kai, Kimiyasu Egami, Toyoaki Murohara, Ayami Ikeda, Suguru Yasuoka, Kensuke Egashira, Toyojiro Matsuishi, Mamiko Kai, Yasufumi Kataoka, Michihiko Kuwano, Tsutomu Imaizumi

    Research output: Contribution to journalArticlepeer-review

    76 Citations (Scopus)

    Abstract

    We investigated whether blocking of monocyte chemoattractant-1 (MCP-1) function would inhibit recruitment of tumor-associated macrophages (TAMs) and prevent tumor angiogenesis and tumor growth of human malignant melanoma. B16-F1 melanoma cells were implanted onto the back of C57BL/6 mice (Day 0). At Day 7, a dominant negative MCP-1 mutant (7ND) gene was transfected in the thigh muscle to make overexpressed 7ND protein secreted into systemic circulation. 7ND treatment inhibited TAM recruitment and partially reduced tumor angiogenesis and tumor growth. Also, 7ND treatment attenuated inductions of tumor necrosis factor-α (TNFα), interleukin-1α (IL-1α), and vascular endothelial growth factor (VEGF) in the stroma and tumor. Melanoma cells expressed not only MCP-1 but also its receptor CCR2. Accordingly, it was suggested that MCP-1 would enhance tumor angiogenesis and early tumor growth in the early stages by inducing TNFα, IL-1α, and VEGF through TAM recruitment and probably the direct autocrine/paracrine effects on melanoma cells.

    Original languageEnglish
    Pages (from-to)279-284
    Number of pages6
    JournalBiochemical and Biophysical Research Communications
    Volume365
    Issue number2
    DOIs
    Publication statusPublished - Jan 11 2008

    All Science Journal Classification (ASJC) codes

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

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