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

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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

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Tumors
Melanoma
Growth
Neoplasms
Macrophages
Therapeutics
Interleukin-1
Vascular Endothelial Growth Factor A
Tumor Necrosis Factor-alpha
CCR2 Receptors
Experimental Melanomas
Chemotactic Factors
Thigh
Inbred C57BL Mouse
Muscle
Monocytes
Genes
Muscles

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mutant MCP-1 therapy inhibits tumor angiogenesis and growth of malignant melanoma in mice. / Koga, Mitsuhisa; Kai, Hisashi; Egami, Kimiyasu; Murohara, Toyoaki; Ikeda, Ayami; Yasuoka, Suguru; Egashira, Kensuke; Matsuishi, Toyojiro; Kai, Mamiko; Kataoka, Yasufumi; Kuwano, Michihiko; Imaizumi, Tsutomu.

In: Biochemical and Biophysical Research Communications, Vol. 365, No. 2, 11.01.2008, p. 279-284.

Research output: Contribution to journalArticle

Koga, M, Kai, H, Egami, K, Murohara, T, Ikeda, A, Yasuoka, S, Egashira, K, Matsuishi, T, Kai, M, Kataoka, Y, Kuwano, M & Imaizumi, T 2008, 'Mutant MCP-1 therapy inhibits tumor angiogenesis and growth of malignant melanoma in mice', Biochemical and Biophysical Research Communications, vol. 365, no. 2, pp. 279-284. https://doi.org/10.1016/j.bbrc.2007.10.182
Koga, Mitsuhisa ; Kai, Hisashi ; Egami, Kimiyasu ; Murohara, Toyoaki ; Ikeda, Ayami ; Yasuoka, Suguru ; Egashira, Kensuke ; Matsuishi, Toyojiro ; Kai, Mamiko ; Kataoka, Yasufumi ; Kuwano, Michihiko ; Imaizumi, Tsutomu. / Mutant MCP-1 therapy inhibits tumor angiogenesis and growth of malignant melanoma in mice. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 365, No. 2. pp. 279-284.
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