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Collagen type XVIII/endostatin is differentially expressed in primary and metastatic colorectal cancers and ovarian carcinomas.
- Source :
-
British journal of cancer [Br J Cancer] 2001 Nov 16; Vol. 85 (10), pp. 1540-5. - Publication Year :
- 2001
-
Abstract
- 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.
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma secondary
Adult
Aged
Biomarkers analysis
Carcinoma genetics
Collagen genetics
Collagen Type XVIII
Colon metabolism
Colorectal Neoplasms genetics
Colorectal Neoplasms secondary
Endostatins
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
In Situ Hybridization
Liver Neoplasms pathology
Male
Middle Aged
Ovarian Neoplasms genetics
Peptide Fragments genetics
RNA, Messenger biosynthesis
RNA, Neoplasm biosynthesis
Transcription, Genetic
Adenocarcinoma metabolism
Carcinoma metabolism
Collagen biosynthesis
Colorectal Neoplasms metabolism
Ovarian Neoplasms metabolism
Peptide Fragments biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0007-0920
- Volume :
- 85
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 11720442
- Full Text :
- https://doi.org/10.1054/bjoc.2001.2143