Contact of high-invasive, but not low-invasive, melanoma cells to native collagen I induces the release of mature cathepsin B
Contact of high-invasive, but not low-invasive, melanoma cells to native collagen I induces the release of mature cathepsin B
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DOI：
10.1002/ijc.21700
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发表时间：
2006-06-01
影响因子：
6.4
通讯作者：
Hunzelmann, N
中科院分区：
文献类型：
--
作者：
Klose, A;Wilbrand-Hennes, A;Hunzelmann, N
恶性肿瘤细胞的转移涉及细胞-细胞和细胞-基质相互作用，调节蛋白水解酶的表达和定位。在本研究中，我们研究了在塑料上或与单体或纤维状 1 型胶原接触的高（MV3）、中（SKmel28）和低侵袭（SKmel23、WM164）人类黑色素瘤细胞系中溶酶体半胱氨酸蛋白酶组织蛋白酶 B 及其天然抑制剂胱抑素 A、B 和 C 的表达和定位。组织蛋白酶 B 的转录水平和天然抑制剂胱抑素的转录水平均未检测到。 B 和 C 因黑色素瘤细胞与 1 型胶原蛋白的相互作用而改变。然而，组织蛋白酶 B 及其抑制剂的蛋白质表达和细胞定位受到显着影响。与低侵袭性细胞相反，高侵袭性细胞在塑料上培养时会持续释放组织蛋白酶 B。此外，侵入细胞与 I 型纤维状胶原蛋白的接触导致两种成熟形式的蛋白酶的释放。使用针对整联蛋白受体 β1 亚基的抑制性抗体进行的扰动研究表明，β1 整联蛋白受体家族在调节组织蛋白酶 B 释放中发挥作用。与低侵袭性细胞相比，两种培养条件下高侵袭性细胞中的胱抑素 B 蛋白表达要低得多。胱抑素 C 的表达在所有细胞中都相当，但细胞与 I 型纤维状胶原蛋白接触诱导了其表达。这些结果强烈暗示细胞-基质相互作用对于调节黑色素瘤细胞中组织蛋白酶 B 定位和活性的关键作用。 (c) 2005 年 Wiley,-Liss, Inc.
Metastasis of malignant tumor cells involves cell-cell and cell-matrix interactions, which regulate the expression and localization of proteolytic enzymes. In the present study, we investigated the expression and localization of the lysosomal cysteine proteinase cathepsin B and its natural inhibitors cystatin A, B and C in high-(MV3), intermediate- (SKmel28) and low-invasive (SKmel23, WM164) human melanoma cell lines grown on plastic or in contact with monomeric or fibrillar collagen type 1. Neither the transcript levels of cathepsin B nor those of the natural inhibitors, cystatin B and C, were altered by the interaction of melanoma cells with collagen type 1. However, protein expression and cellular localization of cathepsin B and its inhibitors were markedly affected. In contrast to low-invasive cells, high-invasive cells constitutively released procathepsin B when cultured on plastic. In addition, contact of invasive cells with fibrillar collagen type I resulted in the release of both mature forms of the protease. Perturbation studies using inhibitory antibodies against the beta 1 subunit of the integrin receptor indicated a role for the beta 1 integrin receptor family in the regulation of cathepsin B release. Cystatin B protein expression was much lower in high-invasive cells in both culture conditions, when compared to low-invasive cells. Cystatin C expression was comparable in all cells, but cell contact to fibrillar collagen type I induced its expression. These results strongly implicate a pivotal role of cell-matrix interactions for the regulation of cathepsin B localization and activity in melanoma cells. (c) 2005 Wiley,-Liss, Inc.