Collagen type XVIII/endostatin is differentially expressed in primary and metastatic colorectal cancers and ovarian carcinomas.
Collagen type XVIII/endostatin is differentially expressed in primary and metastatic colorectal cancers and ovarian carcinomas.
复制标题
胶原蛋白型XVIII/内抑素在原发性和转移性结直肠癌和卵巢癌中差异表达。
DOI：
10.1054/bjoc.2001.2143
复制
发表时间：
2001-11-16
影响因子：
8.8
通讯作者：
Schuppan, D
中科院分区：
文献类型：
--
作者：
Guenther, U;Herbst, H;Bauer, M;Isbert, C;Buhr, H J;Riecken, E O;Schuppan, D
胶原XVIII型（C18）是基底膜的非纤维状胶原。其C末端片段内皮抑制素已被鉴定为血管生成抑制剂。C18主要在正常肝、肝癌肝和肿瘤肝的肝细胞中表达。我们比较了C18 RNA在结肠腺癌转移灶（代表最常发生的肝肿瘤）、正常结肠粘膜、原发性结肠癌和卵巢癌（通常在形态上与结肠癌或转移灶相似）中的表达模式。两个C18特异性RNA探针进行原位杂交结合免疫组化的细胞角蛋白，波形蛋白和内皮标志物CD31，以表征C18表达细胞。C18/endostatin蛋白通过免疫组织化学定位。在结直肠癌及其肝转移中，在内皮细胞和成纤维细胞/肌成纤维细胞中观察到高水平的C18转录物，而癌细胞中几乎不存在C18 RNA。卵巢癌表现出高C18 RNA表达的癌细胞和基质细胞，表明C18在肿瘤间质细胞的转录诱导是独立的癌细胞表达C18的能力。虽然肿瘤细胞衍生的C18在癌症生长调节中的作用仍然未知，但刺激局部强烈表达的C18蛋白水解为内皮抑制素可以为靶向肿瘤治疗提供有吸引力的方法。2001癌症研究运动 http://www.bjcancer.com
Collagen type XVIII (C18) is a nonfibrillar collagen of basement membranes. Its C-terminal fragment, endostatin, has been identified as an inhibitor of angiogenesis. C18 is predominantly expressed by hepatocytes of normal, cirrhotic and neoplastic liver. We compared the patterns of C18 RNA-expression in colonic adenocarcinoma metastases, which represent the most frequently occurring liver tumours, to normal colon mucosa, to primary colon cancers and to ovarian cancers which are often morphologically similar to colonic cancer or metastasis. Two C18-specific RNA-probes were generated to perform in situ hybridization combined with immunohistochemistry for cytokeratin, vimentin and the endothelial marker CD31, in order to characterize the C18-expressing cells. C18/endostatin protein was localized by immunohistology. In colorectal carcinomas and their liver metastases high levels of C18 transcripts were observed in endothelial cells and fibroblasts/myofibroblasts, whereas C18 RNA was virtually absent from carcinoma cells. Ovarian carcinomas displayed high C18 RNA expression both in carcinoma and stromal cells, indicating that induction of C18 transcription in tumour stromal cells is independent of the ability of carcinoma cells to express C18. While the role of tumour cell derived C18 in cancer growth regulation remains unknown, stimulation of proteolysis of the locally strongly expressed C18 to endostatin could offer an attractive approach for a targeted antineoplastic therapy. © 2001 Cancer Research Campaign http://www.bjcancer.com