CXC-chemokines stimulate invasion and chemotaxis in prostate carcinoma cells through the CXCR2 receptor

BACKGROUND. Metastasis of prostate carcinoma requires invasion through the basement membrane, a thin extracellular matrix that underlies the epithelia l cells, which must be breached by tumor cells invading into surrounding ti ssue. The CXC-chemokines, which have been shown to promote the migration of neutrophils and carcinoma cells, are candidates to influence prostate carc inoma-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 compone nt of the basement membrane. RESULTS. PC3 cells responded to IL-8 and GRO alpha with a 1.6-2-fold increa se 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 t he beta(1) integrins were not changed by IL-8, and alpha(6 beta 1) integrin was used for both stimulated and baseline migration. In addition to the in creases in migration and invasion, 2-6-fold transient increases in adhesion on laminin were seen with both IL-8 and GRO alpha. CONCLUSIONS. These results suggest that the CXC-chemokines stimulate migrat ion and invasion in part by altering the activation state of the beta(1) in tegrins. The CXC-chemokines act on prostate carcinoma cells through the CXC R2 receptor to promote behavior important for metastasis, and as such may b e important in prostate carcinoma progression and metastasis. (C) 1999 Wile y-Liss, Inc.