Basal prostate epithelial cells stimulate the migration of prostate cancer cells.
Carcinoma cells in PIN are situated above a layer of basal epithelial cells, which shield the tumor cells from stimulation by factors from the prostate stroma. During progression to invasive carcinoma, the basal cell layer becomes disrupted and tumor cells adhere to the basement membrane. The close proximity of basal epithelial cells to tumor cells in the early stages of prostate oncogenesis raises the possibility that basal epithelial cells participate in tumor cell invasion. Here, we investigated the migration-promoting activity of secreted factors from basal epithelial cells on BPH-1 cells, which we used as an in vitro model of preinvasive prostate cancer cells. We showed that the conditioned medium of basal epithelial cells (PEC-CM) contains adhesion proteins and chemotactic factors that stimulate adhesion, planar polarization, migration, and phosphorylation of Akt and that LY294002 and Wortmannin partially inhibit PEC-CM-triggered migration. We identified laminin-5 as a major migration-stimulating protein for BPH-1 cells in PEC-CM. Laminin-5 induced migration is completely inhibited by LY294002 or Wortmannin. In addition, antibody-depletion of laminin-5 from PEC-CM significantly diminishes the migration of BPH-1 cells. These results demonstrated, that laminin-5 is secreted by basal prostate epithelial cells in vivo and in vitro and stimulates migration of BPH-1 cells through a PI3-kinase dependent mechanism. Altogether, the possibility that basal epithelial cells assist in the invasion of in situ carcinoma cells is supported by the results from our in vitro system.
Yu
Hsiao-Man
HM
Department of Pathology, Weill Medical College of Cornell University, New York, NY, USA.
Frank
Diane E
DE
Zhang
Jie
J
You
Xueke
X
Carter
William G
WG
Knudsen
Beatrice S
BS
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002465:Cell Movement; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019048:Prostatic Intraepithelial Neoplasia / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000097794:Kalinin; C494918:AKT1 protein, human