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

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

doi:10.3892/ijo_00000123

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

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

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

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/SCID/γ_c^null, 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 micro-environment- modification including PAI up-regulation and anti-vascularization in human malignant melanoma.

Original language	English
Pages (from-to)	5-13
Number of pages	9
Journal	International journal of oncology
Volume	34
Issue number	1
DOIs	https://doi.org/10.3892/ijo_00000123
Publication status	Published - 2009
Externally published	Yes

Keywords

Malignant melanoma
Metastasis
Microenvironment
Mouse model
Plasminogen activator
Thrombospondin 2

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3892/ijo_00000123

Cite this

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. (2009). Thrombospondin 2 inhibits metastasis of human malignant melanoma through microenvironment-modification in NOD/SCID/γ_c ^null (NOG) mice. International journal of oncology, 34(1), 5-13. https://doi.org/10.3892/ijo_00000123

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 2009, 'Thrombospondin 2 inhibits metastasis of human malignant melanoma through microenvironment-modification in NOD/SCID/γ_c ^null (NOG) mice', International journal of oncology, vol. 34, no. 1, pp. 5-13. https://doi.org/10.3892/ijo_00000123

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title = "Thrombospondin 2 inhibits metastasis of human malignant melanoma through microenvironment-modification in NOD/SCID/γc null (NOG) mice",

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/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 micro-environment- modification including PAI up-regulation and anti-vascularization in human malignant melanoma.",

keywords = "Malignant melanoma, Metastasis, Microenvironment, Mouse model, Plasminogen activator, Thrombospondin 2",

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T1 - Thrombospondin 2 inhibits metastasis of human malignant melanoma through microenvironment-modification in NOD/SCID/γc null (NOG) mice

AU - Chijiwa, Tsuyoshi

AU - Abe, Yoshiyuki

AU - Ikoma, Norihiro

AU - Yamazaki, Hitoshi

AU - Tsukamoto, Hideo

AU - Suemizu, Hiroshi

AU - Kawai, Kenji

AU - Wakui, Masatoshi

AU - Nishime, Chiyoko

AU - Matsumoto, Hozumi

AU - Matsuyama, Masahiro

AU - Mukai, Masaya

AU - Ueyama, Yoshito

AU - Nakamura, Masato

PY - 2009

Y1 - 2009

N2 - 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/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 micro-environment- modification including PAI up-regulation and anti-vascularization in human malignant melanoma.

AB - 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/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 micro-environment- modification including PAI up-regulation and anti-vascularization in human malignant melanoma.

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KW - Metastasis

KW - Microenvironment

KW - Mouse model

KW - Plasminogen activator

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