CXCL5 promotes prostate cancer progression.
CXCL5 is a proangiogenic CXC-type chemokine that is an inflammatory mediator and a powerful attractant for granulocytic immune cells. Unlike many other chemokines, CXCL5 is secreted by both immune (neutrophil, monocyte, and macrophage) and nonimmune (epithelial, endothelial, and fibroblastic) cell types. The current study was intended to determine which of these cell types express CXCL5 in normal and malignant human prostatic tissues, whether expression levels correlated with malignancy and whether CXCL5 stimulated biologic effects consistent with a benign or malignant prostate epithelial phenotype. The results of these studies show that CXCL5 protein expression levels are concordant with prostate tumor progression, are highly associated with inflammatory infiltrate, and are frequently detected in the lumens of both benign and malignant prostate glands. Exogenous administration of CXCL5 stimulates cellular proliferation and gene transcription in both nontransformed and transformed prostate epithelial cells and induces highly aggressive prostate cancer cells to invade through synthetic basement membrane in vitro. These findings suggest that the inflammatory mediator, CXCL5, may play multiple roles in the etiology of both benign and malignant proliferative diseases in the prostate.
Begley
Lesa A
LA
Department of Urology, University of Michigan, Ann Arbor, MI 48109-0944, USA.
Kasina
Sathish
S
Mehra
Rohit
R
Adsule
Shreelekha
S
Admon
Andrew J
AJ
Lonigro
Robert J
RJ
Chinnaiyan
Arul M
AM
Macoska
Jill A
JA
D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D054365:Chemokine CXCL5 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051766:Early Growth Response Protein 1 / Q000235:genetics; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D046888:Tissue Array Analysis; D014158:Transcription, Genetic / Q000187:drug effects
C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases