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核心蛋白聚糖蛋白在癌巢周边子宫颈癌细胞中的表达与积聚。

Expression and accumulation of lumican protein in uterine cervical cancer cells at the periphery of cancer nests.

作者信息

Naito Zenya, Ishiwata Toshiyuki, Kurban Gulnar, Teduka Kiyoshi, Kawamoto Yoko, Kawahara Kiyoko, Sugisaki Yuichi

机构信息

Department of Pathology, Nippon Medical School, Tokyo 113-8602, Japan.

出版信息

Int J Oncol. 2002 May;20(5):943-8.

Abstract

Lumican is a member of a small leucine-rich proteoglycan (SLRP) family and is reported to be overexpressed during the wound healing process of the cornea, and ischemic and reperfused heart. In the carcinomatous tissues, lumican is overexpressed in human breast and pancreatic cancer tissues. In the present study, we aimed to clarify the expression of lumican mRNA and its protein in human cervical cancer cell lines (CaSki, ME-180 and HeLa cells) and their localization in normal and cancerous human cervical tissues. Reverse transcription-polymerase chain reaction and Western blot analysis revealed the expression of lumican mRNA and its protein in CaSki, ME-180 and HeLa cells. No or weak immunoreactivity of the lumican protein was observed in stroma but not in squamous and ductal cells of non-cancerous uterine cervical tissues. In 21 of 28 (75%) cervical cancer cases, the lumican protein was strongly expressed in cancer cells, and accumulated particularly in cancer cells at the periphery of the cancer nests. It was also expressed in the fibroblasts adjacent to the cancer cells. In situ hybridization analysis revealed that lumican mRNA was not expressed in squamous or ductal epithelial cells in non-cancerous tissues, but was expressed in most cancer cells and stromal fibroblasts in uterine cervical cancer tissues. The lumican protein was not localized in normal squamous or ductal cells close to cancer cells, but its mRNA was strongly expressed in the same cells. To our knowledge, this is the first report on lumican synthesized by squamous cell carcinomas. These findings may indicate that the accumulated lumican protein in cancer cells at the periphery of cancer nests may play roles in the growth or invasion of human cervical cancer cells.

摘要

角膜蛋白聚糖是富含亮氨酸的小分子蛋白聚糖(SLRP)家族的成员,据报道在角膜、缺血再灌注心脏的伤口愈合过程中过表达。在癌组织中,角膜蛋白聚糖在人乳腺癌和胰腺癌组织中过表达。在本研究中,我们旨在阐明角膜蛋白聚糖mRNA及其蛋白在人宫颈癌细胞系(CaSki、ME-180和HeLa细胞)中的表达情况以及它们在人正常宫颈组织和癌组织中的定位。逆转录-聚合酶链反应和蛋白质印迹分析显示CaSki、ME-180和HeLa细胞中存在角膜蛋白聚糖mRNA及其蛋白的表达。在非癌性子宫颈组织的基质中未观察到角膜蛋白聚糖蛋白的免疫反应性或免疫反应性较弱,但在鳞状和导管细胞中未观察到。在28例宫颈癌病例中的21例(75%)中,角膜蛋白聚糖蛋白在癌细胞中强烈表达,尤其在癌巢周边的癌细胞中积累。它也在与癌细胞相邻的成纤维细胞中表达。原位杂交分析显示,角膜蛋白聚糖mRNA在非癌性组织的鳞状或导管上皮细胞中不表达,但在子宫颈癌组织的大多数癌细胞和基质成纤维细胞中表达。角膜蛋白聚糖蛋白不在靠近癌细胞的正常鳞状或导管细胞中定位,但其mRNA在相同细胞中强烈表达。据我们所知,这是关于鳞状细胞癌合成角膜蛋白聚糖的首次报道。这些发现可能表明癌巢周边癌细胞中积累的角膜蛋白聚糖蛋白可能在人宫颈癌细胞的生长或侵袭中起作用。

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