Keratinocyte-derived chemokine induces prostate epithelial hyperplasia and reactive stroma in a novel transgenic mouse model.
BACKGROUND
Interleukin-8 (IL-8) is upregulated in fibrotic and malignant diseases and is a key mediator of proliferative responses. Elevated IL-8 was recently correlated with benign prostatic hyperplasia epithelium and a myofibroblast reactive stroma. Thus, we sought to determine whether overexpressed IL-8 and keratinocyte-derived chemokine (KC), the functional murine homolog of IL-8, induce prostate epithelial hyperplasia and a reactive phenotype.


METHODS
Transgenic mice that overexpress KC within prostate epithelia and xenograft models with engineered human cells that overexpress IL-8 were developed.


RESULTS
Overexpression of KC in transgenic mice produced hyperplastic prostate epithelial acini associated with a periacinar reactive stroma. KC induced an altered epithelial/stroma proliferation index ratio, increased acini diameter, epithelial infolding, and expression of prototypical reactive stroma markers. Overexpression of IL-8 in normal human prostate epithelial xenografts correlated with elevated epithelial proliferation index and altered morphology. Elevated human prostate stromal and epithelial cell proliferation, nodule-like morphology and increased xenograft survival were observed in IL-8-overexpressing orthotopic xenografts.


CONCLUSIONS
Together, these data demonstrate that overexpression of IL-8/KC results in a prostate epithelial hyperplasia with an associated reactive stroma phenotype. The novel transgenic mouse and human xenograft models described here may be useful in dissecting key mechanisms of IL-8 induced prostate hyperplasia and reactive stroma.
Schauer
Isaiah G
IG
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
Ressler
Steven J
SJ
Rowley
David R
DR
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D010641:Phenotype; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous
D018925:Chemokines; D016209:Interleukin-8; C074302:keratinocyte-derived chemokines