Matriptase and HAI-1 are expressed by normal and malignant epithelial cells in vitro and in vivo
Matriptase and HAI-1 are expressed by normal and malignant epithelial cells in vitro and in vivo
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DOI：
10.1016/s0002-9440(10)64081-3
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发表时间：
2001-04-01
影响因子：
6
通讯作者：
Lin, CY
中科院分区：
文献类型：
--
作者：
Oberst, M;Anders, J;Lin, CY
间质蛋白酶及其同源物Kunitz型丝氨酸蛋白酶抑制剂HAI-1包含新表征的细胞外基质降解蛋白酶系统，其可充当其它蛋白酶和潜在生长因子的上皮膜活化剂。在乳腺癌细胞、永生化乳腺上皮细胞和人乳中均检测到酶和抑制剂，但在培养的成纤维细胞和纤维肉瘤细胞中均未检测到。为了检验该系统由正常乳腺上皮、浸润性乳腺癌和上皮来源的其他癌症（癌）表达而不在间充质来源的癌症中表达的假设，我们扩展了我们的间质蛋白酶和HAI-1的体外和体内表达分析。间质蛋白酶和HAI-1的蛋白质和mRNA水平上检测到的依赖性和非依赖性培养的乳腺癌细胞，这种表达与上皮标志物E-cadherin或ZO-1的表达相关。然而，所测试的表达间充质标志物波形蛋白的乳腺癌细胞系均不表达间质蛋白酶或HAI-1，这与该系统的上皮选择性表达一致。蛋白质印迹分析表明，matriptase的表达在原发性乳腺癌、妇科癌和结肠癌中观察到，但在各种来源和组织学分级的基质源性卵巢肿瘤和人肉瘤中未观察到。间质蛋白酶和HAI-1的上皮选择性表达通过免疫组织化学和原位杂交进一步证实在人乳腺癌中，其中在癌细胞和周围正常乳腺上皮中发现蛋白酶和抑制剂的表达。恶性上皮细胞在体内表达间质蛋白酶/HAI-1系统表明该蛋白酶在上皮恶性肿瘤的病理生理学的多个方面（包括侵袭和转移）中可能起作用。
Matriptase and its cognate, Kunitz-type serine protease inhibitor, HAI-1, comprise a newly characterized extracellular matrix-degrading protease system that may function as an epithelial membrane activator for other proteases and latent growth factors. both enzyme and inhibitor have been detected in breast cancer cells, immortalized mammary epithelial cells, and human milk, but not in cultured fibroblasts nor in fibrosarcoma cells. To test the hypothesis that this system is expressed by normal breast epithelium, Invasive breast cancers, and other cancers of an epithelial origin (carcinomas) but not in cancers of a mesenchymal origin, we have expanded our expression analysis of matriptase and HAI-1 in vitro and in vivo. Matriptase and HAI-1 were detected at the protein and mRNA levels both in hormone-dependent and hormone-independent cultured breast cancer cells, and this expression correlated with the expression of the epithelial markers E-cadherin or ZO-1. However, none of the breast cancer cell lines tested that express the mesenchymal marker vimentin express matriptase or HAI-1, consistent with an epithelial-selective expression of this system. Expression of matriptase, as determined by Western blot analysis, was observed in primary human breast, gynecological, and colon carcinomas, but not in stromal-derived ovarian tumors and human sarcomas of various origins and histological grades. The epithelial-selective expression of matriptase and HAI-1 was further confirmed in human breast cancers by immunohistochemistry and In situ hybridization, where the expression of the protease and the inhibitor were found in the carcinoma cells and in surrounding normal breast epithelia. The expression of the matriptase/HAI-1 system by malignant epithelial cells in vivo suggests a possible role for this protease in multiple aspects of the pathophysiology of epithelial malignancy, including invasion and metastasis.