DeCastro R, Zhang Y, Guo H, Kataoka H, Gordon M K, Toole B p, Biswas G
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts, USA.
J Invest Dermatol. 1996 Jun;106(6):1260-5. doi: 10.1111/1523-1747.ep12348959.
Increased levels of matrix metalloproteinases are associated with tissue degradation and remodeling during tumor invasion and wound healing. In both processes, there is evidence that cell interactions between fibroblasts and tumor cells or keratinocytes lead to increases in metalloproteinase production. We have previously isolated and purified a tumor cell surface protein, EMMPRIN (extracellular matrix metalloproteinase inducer), which stimulates production of interstitial collagenase, gelatinase A, and stromelysin-1 by fibroblasts, and we have obtained cDNA clones that encode the EMMPRIN protein from LX-1 human lung carcinoma cells. In this study we report immunolocalization of EMMPRIN around the surface of human keratinocytes in vitro and in vivo, and isolation of cDNAs that encode the entire open reading frame for EMMPRIN from a human keratinocyte library. Comparison of the EMMPRIN cDNAs from normal human keratinocytes and LX-1 human tumor cells by nucleotide sequence analysis, expression of the recombinant proteins, and in vitro translation using the cDNAs from the two sources indicate that they express very similar forms of EMMPRIN. Native EMMPRIN isolated directly from extracts of keratinocytes, however, is slightly smaller in size and is present at a lower concentration compared with that from LX-1 tumor cells. These results establish the presence of EMMPRIN in the normal epidermis and raise the possibility of its involvement in regulation of matrix remodeling at the epidermal-dermal interface.
基质金属蛋白酶水平升高与肿瘤侵袭和伤口愈合过程中的组织降解及重塑相关。在这两个过程中，有证据表明成纤维细胞与肿瘤细胞或角质形成细胞之间的细胞相互作用会导致金属蛋白酶产生增加。我们之前已分离并纯化了一种肿瘤细胞表面蛋白，即细胞外基质金属蛋白酶诱导剂（EMMPRIN），它可刺激成纤维细胞产生间质胶原酶、明胶酶A和基质溶解素-1，并且我们已从LX-1人肺癌细胞中获得了编码EMMPRIN蛋白的cDNA克隆。在本研究中，我们报告了EMMPRIN在体外和体内人角质形成细胞表面周围的免疫定位，以及从人角质形成细胞文库中分离出编码EMMPRIN完整开放阅读框的cDNA。通过核苷酸序列分析、重组蛋白表达以及使用来自这两种来源的cDNA进行体外翻译，比较正常人角质形成细胞和LX-1人肿瘤细胞的EMMPRIN cDNA，结果表明它们表达非常相似形式的EMMPRIN。然而，直接从角质形成细胞提取物中分离的天然EMMPRIN，其大小略小，与来自LX-1肿瘤细胞的EMMPRIN相比，其浓度也较低。这些结果证实了正常表皮中存在EMMPRIN，并增加了其参与调节表皮-真皮界面基质重塑的可能性。
