CANINE OSTEOSARCOMA CELLS EXPRESS MMP-9 THROUGH CELL-MATRIX

犬骨肉瘤细胞通过细胞基质表达 MMP-9

• 批准号: 10660280
• 负责人: ARAI Katsuhiko
• 金额: $ 2.3万
• 依托单位: Tokyo University of Agriculture & Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10660280/
• 关键词: MMP; TUMOR; INTEGRIN; SIGNAL TRANSDUCTION; がん; 転移

To investigate the participation of MMP-9 in the formation of lung metastasis, we have established an animal model for lung metastasis by the injection of osteosarcoma (OS) cells into mammary fad pad of SCID mice. Gelatinzymography revealed a great deal of MMP-9 secreted by the lung tissues containing metastatic lesions, whereas only MMP-2 was detected in 'hypothetic' origin these results suggested that OS cells could acquire the ability of MMP-9 expression during tumor invasion and metastasis. Therefore, we examined the mechanism of MMP-9 expression under several culture condition in vitro. In monolayer culture of OS cells on several extracellular matrix, MMP-9 was not detected by gelatin zymography, while MMP-2 was constantly expressed. When OS cells were cultivated in type I collagen gel, MMP-9 was apparently detected in addition of MMP-2. The expression of MMP-9 in collagen gel was down-regulated by anti-integrin antibodies and cytochalasin D. Thus, we suggested that the expression of MMP-9 by OS cells was regulated through integrin-mediated cell-matrix interaction and following actin polymerization.

为探讨MMP-9在骨肉瘤肺转移形成中的作用，本研究通过将骨肉瘤（OS）细胞注射到SCID小鼠的乳腺脂肪垫中，建立了骨肉瘤肺转移的动物模型。明胶酶谱显示，转移灶周围肺组织大量分泌MMP-9，而“假设”来源的肺组织仅表达MMP-2，提示OS细胞在肿瘤侵袭转移过程中获得表达MMP-9的能力。因此，我们研究了MMP-9在体外培养条件下的表达机制。在几种细胞外基质上的OS细胞单层培养中，明胶酶谱法未检测到MMP-9，而MMP-2持续表达。当OS细胞在I型胶原凝胶中培养时，除了MMP-2外，还明显检测到MMP-9。抗整合素抗体和细胞松弛素D可下调胶原凝胶中MMP-9的表达。因此，我们认为，MMP-9的表达由OS细胞通过整合素介导的细胞基质相互作用和以下肌动蛋白聚合调节。

项目成果

Ohshima K, Kishi H, Itoh M, Watanabe G, Arai K, Uehara K, Groome NP, Taya K: "Secrtion of inhibin A, inhibin B and inhibin pro-alphaC during the oestrous cycle of the golden hamster (Mesocricetus auratus)"J. Endocrinol. 162. 451-456 (1999)

Ohshima K、Kishi H、Itoh M、Watanabe G、Arai K、Uehara K、Groome NP、Taya K：“金仓鼠 (Mesocricetus auratus) 发情周期中抑制素 A、抑制素 B 和抑制素前体 αC 的部分”

TANAKA et al.: "Matrix metalloproteinase-9 production, a newly identified function of mast cell progenitors, is downregulated by c-kit receptor activation"Blood. 94. 2390-2395 (1999)

TANAKA 等人：“基质金属蛋白酶 9 的产生是肥大细胞祖细胞的一种新发现的功能，可通过 c-kit 受体激活来下调”血液。

新井 他: "細胞外マトリックス研究法全6巻"コラーゲン技術研修会. 789 (1998)

Arai等人：“细胞外基质研究方法，6卷”胶原技术研讨会789（1998）。

K. ARAI., K. OHSHIMA, G. WATANABE, K. ARAI, K. UEHARA, K. TAYA: "Inhibition of ovarian follicular developed associated with a decrease in luterinizing hormone levels during the estrous cycle of the rat"Endocrine J., 1998. 45. 539-546 (1998)

K. ARAI.、K. OHSHIMA、G. WATANABE、K. ARAI、K. UEHARA、K. TAYA：“卵巢卵泡发育的抑制与大鼠动情周期期间黄体生成素水平的降低有关”Endocrine J.

A. TANAKA, K. ARAI.,Y. KITAMURA and H. MATSUDA: "Matrix metalloproteinase-9 production, a newly Identified function of mast cell progenitors, is downregulated by c-kit receptor activation"Blood. 94. 2390-2395 (1999)

A. 田中, K. 新井.,Y.