Open Access

Thrombospondin 2 inhibits metastasis of human malignant melanoma through microenvironment-modification in NOD/SCID/γCnull (NOG) mice

  • Authors:
    • Tsuyoshi Chijiwa
    • Yoshiyuki Abe
    • Norihiro Ikoma
    • Hitoshi Yamazaki
    • Hideo Tsukamoto
    • Hiroshi Suemizu
    • Kenji Kawai
    • Masatoshi Wakui
    • Chiyoko Nishime
    • Hozumi Matsumoto
    • Masahiro Matsuyama
    • Masaya Mukai
    • Yoshito Ueyama
    • Masato Nakamura
  • View Affiliations

  • Published online on: January 1, 2009     https://doi.org/10.3892/ijo_00000123
  • Pages: 5-13
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Abstract

Thrombospondin (TSP) 2 interacts with matrix metalloproteinases (MMPs) and matrix serine proteases such as plasminogen activator (PA). Malignant melanoma is an aggressive human neoplasm showing aggressive metastatic features. We examined the effects of TSP2 gene introduction in the human malignant melanoma cell line A375. We established three clones transfected with human TSP2 (A375/TSP2). The in vitro invasiveness was remarkably suppressed (42-61%) in the TSP2-transfectants, while growth properties were preserved. The A375/TSP2 showed significantly decreased liver metastatic potential (liver weight: 3.88±0.30 g in A375/TSP2, 7.07±0.67 g in vector-transfectant (A375/V), p<0.01, Mann-Whitney U test) in super immuno-deficient mice (NOD/SCID/γcnull, NOG). The PA inhibitor-1 (PAI-1) and PAI-2 mRNAs were significantly overexpressed in A375/TSP2. The increased activities of PAI-1 and PAI-2 were confirmed by reverse zymography. The vascularity of metastatic lesions was significantly decreased in A375/TSP2 (vascular density: 0.62±0.15% in A375/TSP2, 4.96±0.61% in A375/V, p<0.01, Welch test). These results suggest that TSP2 suppresses hematogenous metastasis through microenvironment-modification including PAI up-regulation and anti-vascularization in human malignant melanoma.

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January 2009
Volume 34 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Chijiwa, T., Abe, Y., Ikoma, N., Yamazaki, H., Tsukamoto, H., Suemizu, H. ... Nakamura, M. (2009). Thrombospondin 2 inhibits metastasis of human malignant melanoma through microenvironment-modification in NOD/SCID/γCnull (NOG) mice. International Journal of Oncology, 34, 5-13. https://doi.org/10.3892/ijo_00000123
MLA
Chijiwa, T., Abe, Y., Ikoma, N., Yamazaki, H., Tsukamoto, H., Suemizu, H., Kawai, K., Wakui, M., Nishime, C., Matsumoto, H., Matsuyama, M., Mukai, M., Ueyama, Y., Nakamura, M."Thrombospondin 2 inhibits metastasis of human malignant melanoma through microenvironment-modification in NOD/SCID/γCnull (NOG) mice". International Journal of Oncology 34.1 (2009): 5-13.
Chicago
Chijiwa, T., Abe, Y., Ikoma, N., Yamazaki, H., Tsukamoto, H., Suemizu, H., Kawai, K., Wakui, M., Nishime, C., Matsumoto, H., Matsuyama, M., Mukai, M., Ueyama, Y., Nakamura, M."Thrombospondin 2 inhibits metastasis of human malignant melanoma through microenvironment-modification in NOD/SCID/γCnull (NOG) mice". International Journal of Oncology 34, no. 1 (2009): 5-13. https://doi.org/10.3892/ijo_00000123