Abstract 1501: Prostate-specific antigen cleaves nidogen-1
| Autor: | Hannu Koistinen, Johanna Mattsson, Ulf-Håkan Stenman, Suvi Ravela |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Tube formation
Basement membrane 0303 health sciences Cancer Research biology Chemistry Molecular biology In vitro Fibronectin Extracellular matrix 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Oncology Laminin 030220 oncology & carcinogenesis biology.protein medicine Human umbilical vein endothelial cell Endostatin 030304 developmental biology |
| Zdroj: | Cancer Research. 71:1501-1501 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Prostate-specific antigen (PSA or kallikrein-related peptidase 3, KLK3) is a chymotrypsin-like serine protease expressed in the prostate and secreted into seminal fluid. Several studies have demonstrated that PSA exerts anti-angiogenic activity in vitro and in vivo. Using a human umbilical vein endothelial cell (HUVEC) tube formation model, where the cells were grown on Matrigel™ basement membrane preparation, we recently showed that the enzymatic activity of PSA is essential for its anti-angiogenic function. Previously, PSA has been shown to cleave components of extracellular matrix (ECM), e.g., laminin and fibronectin, as well as unidentified proteins in Matrigel™. Proteolytic products of some ECM proteins, such as collagen XVIII-fragment endostatin, are known to be anti-angiogenic. Cleavage of ECM is also crucial for cancer cell invasion. We studied the PSA-generated protein fragments derived from Matrigel™ and aimed to characterize their anti-angiogenic activity. PSA was purified from seminal fluid and incubated with Matrigel™ for 24 h at 37°C. The resulting proteolytic fragments were analyzed by SDS-PAGE and mass spectrometry. Recombinant human nidogen-1 (also known as entactin) was incubated with PSA for 18 h at 37°C and the fragments were analyzed by SDS-PAGE followed by silver staining. The effect of nidogen-1 fragments was studied in the HUVEC tube formation model. We found that PSA cleaves nidogen-1 in Matrigel™. This was confirmed by using recombinant nidogen-1. The nidogen-1 fragments, however, did not have any anti-angiogenic effect on HUVECs in the tube formation model. We conclude that the cleavage of nidogen-1 by PSA may lead to disruption of basement membrane structure and, thus, may inhibit HUVEC tube formation as well as facilitate cancer cell invasion. The nidogen-1 fragments per se do not mediate the anti-angiogenic function of PSA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1501. doi:10.1158/1538-7445.AM2011-1501 |
| Databáze: | OpenAIRE |
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