Stromal antiapoptotic paracrine loop in perineural invasion of prostatic carcinoma.
Caveolin-1 (cav-1) is a major scaffolding component of cell membrane invaginations (caveolae). It is involved in sequestering numerous effectors and signaling molecules and has antiapototic activities in prostate cancer. Perineural invasion (PNI) is associated with decreased apoptosis of cancer cells both in human tissues and the in vitro PNI model. We show here that stromal (perineurium) production of cav-1 is involved in a paracrine antiapoptotic loop in PNI. Transforming growth factor-beta1 is up-regulated in the cancer cells as they approach the nerve and is thought to up-regulate cav-1 in the perineurium of nerves with prostate cancer. Cav-1 is then secreted into the microenvironment and used by prostate cancer cells to inhibit apoptosis. In the in vitro PNI model, this phenomenon is partially reversed by neutralizing cav-1 antibodies or using ganglia from cav-1 knockout mice. Our results show a novel paracrine mechanism used by the prostate cancer in PNI to increase their proliferative activity and decrease apoptosis.
Ayala
Gustavo E
GE
Departments of Pathology, Urology, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. gagyala@bcm.tmc.edu
Dai
Hong
H
Tahir
Salahaldin A
SA
Li
Rile
R
Timme
Terry
T
Ittmann
Michael
M
Frolov
Anna
A
Wheeler
Thomas M
TM
Rowley
David
D
Thompson
Timothy C
TC
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D051242:Caveolin 1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010525:Peripheral Nerves / Q000378:metabolism; D011467:Prostate / Q000294:innervation*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation
D000906:Antibodies; D051242:Caveolin 1; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1