Journal article
Molecular mediators of angiogenesis in bladder cancer
Cancer research (Chicago, Ill.), Vol.58(6), pp.1298-1304
03/15/1998
PMID: 9515819
Abstract
Bladder tumors are characterized by markedly increased angiogenesis when compared to the normal urothelium (NU) from which they are derived. Here, we use both cultured cells and immunohistochemistry to demonstrate a primary regulatory role for thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, in the development of bladder tumor angiogenesis. Secretions from bladder cancer (CA) cells stimulated endothelial cell migration and corneal neovascularization, whereas those from NU cells were inhibitory. The antiangiogenic activity of NU cells was primarily due to secreted TSP-1 because neutralizing antibodies completely relieved the inhibition. Neutralizing antibodies to several putative angiogenesis inducers identified vascular endothelial growth factor (VEGF) and, to a lesser extent, basic fibroblast growth factor as the primary inducers secreted by bladder cancer cells. The secretion of TSP-1 by low- and high-grade cancer cells was reduced >94% when compared to NU cells, and this loss of inhibitory TSP-1 accounted for the development of an angiogenic phenotype because both NU cells and cancer cells secreted similar levels of total stimulatory activity and VEGF. Immunohistochemistry showed that TSP-1 was significantly reduced in all grades of bladder cancer when compared to NU, whereas VEGF staining remained relatively constant. Taken together, these data suggest that down-regulation of TSP-1 secretion is a key event in the switch from an antiangiogenic to an angiogenic phenotype, which occurs early in the development of bladder cancer.
Details
- Title: Subtitle
- Molecular mediators of angiogenesis in bladder cancer
- Creators
- S C Campbell - Department of Urology, R. H. Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611, USA. sc-campbell@nwu.eduO V VolpertM IvanovichN P Bouck
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.58(6), pp.1298-1304
- Publisher
- United States
- PMID
- 9515819
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Grant note
- CA64239 / NCI NIH HHS K12-DK02194-03 / NIDDK NIH HHS CA52750 / NCI NIH HHS
- Language
- English
- Date published
- 03/15/1998
- Academic Unit
- Pathology
- Record Identifier
- 9984047865102771
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