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 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 GROalpha 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 beta(1) integrins were not changed by IL-8, and alpha(6beta1) 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 GROalpha.


CONCLUSIONS
These results suggest that the CXC-chemokines stimulate migration and invasion in part by altering the activation state of the beta(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.
Reiland
J
J
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Furcht
L T
LT
McCarthy
J B
JB
D000595:Amino Acid Sequence; D001485:Basement Membrane; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology; D019743:Chemokines, CXC / Q000494:pharmacology*; D002633:Chemotaxis; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000494:pharmacology; D007797:Laminin / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D014407:Tumor Cells, Cultured
D019743:Chemokines, CXC; D016209:Interleukin-8; D007797:Laminin