NDLI: Tumor suppression in human skin carcinoma cells by chromosome 15 transfer or thrombospondin-1 overexpression through halted tumor vascularization.

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Tumor suppression in human skin carcinoma cells by chromosome 15 transfer or thrombospondin-1 overexpression through halted tumor vascularization.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Popp, S. Stanbridge, E. J. Bleuel, K. Boukamp, P. Fusenig, N. E.
Description	Author Affiliation: Bleuel K ( Division of Carcinogenesis and Differentiation, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.);
Abstract	The development of skin carcinomas presently is believed to be correlated with mutations in the p53 tumor suppressor and ras gene as well as with the loss of chromosome 9. We now demonstrate that, in addition, loss of chromosome 15 may be a relevant genetic defect. Reintroduction of an extra copy of chromosome 15, but not chromosome 4, into the human skin carcinoma SCL-I cells, lacking one copy of each chromosome, resulted in tumor suppression after s.c. injection in mice. Transfection with thrombospondin-1 (TSP-1), mapped to 15q15, induced the same tumor suppression without affecting cell proliferation in vitro or in vivo. Halted tumors remained as small cysts encapsulated by surrounding stroma and blood vessels. These cysts were characterized by increased TSP-1 matrix deposition at the tumor/stroma border and a complete lack of tumor vascularization. Coinjection of TSP-1 antisense oligonucleotides drastically reduced TSP-1 expression and almost completely abolished matrix deposition at the tumor/stroma border. As a consequence, the tumor phenotype reverted to a well vascularized, progressively expanding, solid carcinoma indistinguishable from that induced by the untransfected SCL-I cells. Thus, these data strongly suggest TSP-1 as a potential tumor suppressor on chromosome 15. The data further propose an unexpected mechanism of TSP-1-mediated tumor suppression. Instead of interfering with angiogenesis in general, in this system TSP-1 acts as a matrix barrier at the tumor/stroma border, which, by halting tumor vascularization, prevents tumor cell invasion and, thus, tumor expansion.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	5
Volume Number	96
Language	English
Publisher	National Academy of Sciences
Publisher Date	1999-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Carcinoma, Squamous Cell Genetics Chromosomes, Human, Pair 15 Skin Neoplasms Blood Supply Thrombospondin 1 Animals Pathology Prevention & Control Cell Division Chromosomes, Human, Pair 4 Gene Transfer Techniques Mice Mice, Nude Necrosis Neovascularization, Pathologic Physiopathology Oligonucleotides, Antisense Pharmacology Recombinant Proteins Biosynthesis Stromal Cells Transfection Tumor Cells, Cultured Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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