CXC-chemokines stimulate invasion and chemotaxis in prostate carcinoma cells through the CXCR2 receptor
β Scribed by Reiland, Jane; Furcht, Leo T.; McCarthy, James B.
- Book ID
- 101224833
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 295 KB
- Volume
- 41
- Category
- Article
- ISSN
- 0270-4137
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β¦ Synopsis
BACKGROUND. Metastasis of prostate carcinoma requires invasion through the basement membrane, a thin extracellular matrix that underlies the epithelial cells, which must be breached by tumor cells invading into surrounding tissue. The CXC-chemokines, which have been shown to promote the migration of neutrophils and carcinoma cells, are candidates to influence prostate carcinoma-cell invasion. METHODS. CXC-chemokines were examined for the ability to stimulate prostate cell line PC3 invasion in vitro through a reconstituted basement membrane and long-term migration and short-term adhesion to laminin, a major component of the basement membrane. RESULTS. PC3 cells responded to IL-8 and GROβ£ with a 1.6-2-fold increase in invasion through reconstituted basement membrane. A corresponding 2-3-fold increase in chemotaxis toward IL-8 and GROa was seen on laminin. Anti-CXCR2 antibody inhibited IL-8-stimulated migration. Expression levels of the β€ 1 integrins were not changed by IL-8, and β£ 6β€1 integrin was used for both stimulated and baseline migration. In addition to the increases in migration and invasion, 2-6-fold transient increases in adhesion on laminin were seen with both IL-8 and GROβ£. CONCLUSIONS. These results suggest that the CXC-chemokines stimulate migration and invasion in part by altering the activation state of the β€ 1 integrins. The CXC-chemokines act on prostate carcinoma cells through the CXCR2 receptor to promote behavior important for metastasis, and as such may be important in prostate carcinoma progression and metastasis.
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