Expression of hyaluronidase by tumor cells induces angiogenesis in vivo
Expression of hyaluronidase by tumor cells induces angiogenesis in vivo
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DOI：
10.1073/pnas.93.15.7832
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发表时间：
1996-07-23
影响因子：
11.1
通讯作者：
Sy, MS
中科院分区：
文献类型：
--
作者：
Liu, DC;Pearlman, E;Sy, MS
透明质酸是一种存在于细胞外基质中的蛋白多糖，对维持组织结构很重要。透明质酸的解聚可能促进肿瘤侵袭。此外，已报道透明质酸的寡糖诱导血管生成。我们在此报道，转移性黑色素瘤、结肠癌、胶质母细胞瘤细胞系和结直肠癌患者的bg肿瘤活检组织表达类似于人类精子的透明质酸酶，但正常结肠组织不表达。此外，血管生成由透明质酸酶（+）肿瘤细胞而不是透明质酸酶（-）肿瘤细胞诱导，并且可以被透明质酸酶抑制剂阻断。因此，肿瘤细胞使用透明质酸酶作为“分子破坏者”之一，以去除透明质酸以促进侵袭。因此，透明质酸的分解产物可以通过诱导血管生成进一步促进肿瘤建立。肿瘤细胞上的透明质酸酶可能为抗肿瘤药物提供靶点。
Hyaluronic acid is a proteoglycan present in the extracellular matrix and is important for the maintenance of tissue architecture. Depolymerization of hyaluronic acid may facilitate tumor invasion. In addition, oligosaccharides of hyaluronic acid have been reported to induce angiogenesis. We report here that a hyaluronidase similar to the one on human sperm is expressed by metastatic human melanoma, colon carcinoma, and glioblastoma cell lines and bg tumor biopsies from patients with colorectal carcinomas, but not by tissues from normal colon. Moreover, angiogenesis is induced by hyaluronidase(+) tumor cells but not hyaluronidase(-) tumor cells and can be blocked by an inhibitor of hyaluronidase. Tumor cells thus use hyaluronidase as one of the ''molecular saboteurs') to depolymerize hyaluronic acid to facilitate invasion. As a consequence, breakdown products of hyaluronic acid can further promote tumor establishment by inducing angiogenesis. Hyaluronidase on tumor cells may provide a target for anti-neoplastic drugs.