Nonapical and cytoplasmic expression of interleukin-8, CXCR1, and CXCR2 correlates with cell proliferation and microvessel density in prostate cancer.
OBJECTIVE
We characterized interleukin-8 (IL-8) and IL-8 receptor expression (CXCR1 and CXCR2) in prostate cancer to address their significance to this disease.


METHODS
Immunohistochemistry was conducted on 40 cases of human prostate biopsy containing histologically normal and neoplastic tissue, excised from patients with locally confined or invasive androgen-dependent prostate cancer, and 10 cases of transurethral resection of the prostate material from patients with androgen-independent disease.


RESULTS
Weak to moderate IL-8 expression was strictly localized to the apical membrane of normal prostate epithelium. In contrast, membranous expression of IL-8, CXCR1, and CXCR2 was nonapical in cancer cells of Gleason pattern 3 and 4, whereas circumferential expression was present in Gleason pattern 5 and androgen-independent prostate cancer. Each of IL-8, CXCR1, and CXCR2 were also increasingly localized to the cytoplasm of cancer cells in correlation with advancing stage of disease. Cytoplasmic expression (but not apical membrane expression) of IL-8 in Gleason pattern 3 and 4 cancer correlated with Ki-67 expression (R = 0.79; P < 0.001), cyclin D1 expression (R = 0.79; P < 0.001), and microvessel density (R = 0.81; P < 0.001). In vitro studies on androgen-independent PC3 cells confirmed the mitogenic activity of IL-8, increasing the rate of cell proliferation through activation of both CXCR1 and CXCR2 receptors.


CONCLUSIONS
We propose that the concurrent increase in IL-8 and IL-8 receptor expression in human prostate cancer induces autocrine signaling that may be functionally significant in initiating and promoting the progression of prostate cancer by underpinning cell proliferation and angiogenesis.
Murphy
Catherine
C
Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast, Northern Ireland.
McGurk
Maryalice
M
Pettigrew
Johanna
J
Santinelli
Alfredo
A
Mazzucchelli
Roberta
R
Johnston
Patrick G
PG
Montironi
Rodolfo
R
Waugh
David J J
DJ
D000368:Aged; D000728:Androgens / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001706:Biopsy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011467:Prostate / Q000737:chemistry / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis
D000728:Androgens; D014408:Biomarkers, Tumor; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D019938:Cyclin D1