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反应性基质成纤维细胞的细胞表面糖蛋白作为人类上皮癌潜在的抗体靶点

Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers.

作者信息

Garin-Chesa P, Old L J, Rettig W J

机构信息

Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

出版信息

Proc Natl Acad Sci U S A. 1990 Sep;87(18):7235-9. doi: 10.1073/pnas.87.18.7235.

Abstract

The F19 antigen is a cell surface glycoprotein (Mr, 95,000) of human sarcomas and proliferating, cultured fibroblasts that is absent from resting fibroblasts in normal adult tissues. Normal and malignant epithelial cells are also F19-. The present immunohistochemical study describes induction of F19 in the reactive mesenchyme of epithelial tumors. F19+ fibroblasts were found in primary and metastatic carcinomas, including colorectal (18 of 18 cases studied), breast (14/14), ovarian (21/21), bladder (9/10), and lung carcinomas (13/13). In contrast, the stroma of benign colorectal adenomas, fibrocystic disease and fibroadenomas of breast, benign prostate hyperplasia, in situ bladder carcinomas, and benign ovarian tumors showed no or only moderate numbers of F19+ fibroblasts. Analysis of dermal incision wounds revealed that F19 is strongly induced during scar formation. Comparison of F19 with the extracellular matrix protein tenascin, a putative marker of tumor mesenchyme, showed a cellular staining pattern for F19 vs. the extracellular matrix pattern for tenascin and widespread expression of tenascin in F19- normal tissues and benign tumors. Our results suggest that the F19+ phenotype correlates with specialized fibroblast functions in wound healing and malignant tumor growth. Because of its abundance in tumor mesenchyme, F19 may serve as a target for antibodies labeled with radioisotopes or toxic agents, or inflammatogenic antibodies, in carcinoma patients.

摘要

F19抗原是一种人类肉瘤和增殖性培养成纤维细胞的细胞表面糖蛋白(分子量95,000),在正常成人组织的静止成纤维细胞中不存在。正常和恶性上皮细胞也不表达F19。本免疫组织化学研究描述了上皮肿瘤反应性间充质中F19的诱导情况。在原发性和转移性癌中发现了F19阳性的成纤维细胞,包括结直肠癌(18例研究病例中的18例)、乳腺癌(14/14)、卵巢癌(21/21)、膀胱癌(9/10)和肺癌(13/13)。相比之下,良性结直肠腺瘤、乳腺纤维囊性疾病和纤维腺瘤、良性前列腺增生、原位膀胱癌以及良性卵巢肿瘤的间质中未发现或仅发现少量F19阳性成纤维细胞。对皮肤切口伤口的分析表明,F19在瘢痕形成过程中被强烈诱导。将F19与细胞外基质蛋白腱生蛋白(一种肿瘤间充质的假定标志物)进行比较,结果显示F19呈细胞染色模式,而腱生蛋白呈细胞外基质模式,且腱生蛋白在F19阴性的正常组织和良性肿瘤中广泛表达。我们的结果表明,F19阳性表型与伤口愈合和恶性肿瘤生长中特殊的成纤维细胞功能相关。由于其在肿瘤间充质中含量丰富,F19可能成为癌患者中用放射性同位素或有毒剂标记的抗体或炎性抗体的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5904/54718/5b83f6ef753e/pnas01043-0317-a.jpg

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