Osteopontin mediates dense culture-induced proliferation and adhesion of prostate tumour cells: role of protein kinase C, p38 mitogen-activated protein kinase and calcium.
Cells growing in high density were observed to undergo a variety of responses due to cell-cell contact, pericellular hypoxia, etc. In order to investigate the influence of cell density on cell proliferation and adhesion and to elucidate possible mechanisms, we tested the growth ability of human prostate tumour (PC-3M) cells in dense culture and the influences of density on cell adhesion. Our results demonstrate that increasing cell density exerted stress on PC-3M cells, which decreased cell proliferation in dense cultures, but tended to facilitate tumour metastasis since cell adhesion ability was elevated and the cells showed an increased growth rate after being moved to a favourable growth environment. We conclude that higher cell density-mediated pericellular hypoxia was an important factor inducing expression of the intrinsic hypoxia marker osteopontin, another mechanism contributing to cell adhesion enhancement in PC-3M cells. In addition, cell density enhanced adhesion ability due to the activation of p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase C. Intracellular calcium also played positive roles at least partially through activating p38 MAPK.
Zhou
Hong
H
Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing, China.
Lu
Ning
N
Chen
Zhi-Qiang
ZQ
Song
Qian-Liu
QL
Yu
He-Ming
HM
Li
Xue-Jun
XJ
D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D018929:Cell Culture Techniques; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D053495:Osteopontin / Q000096:biosynthesis / Q000502:physiology*; D011471:Prostatic Neoplasms; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D004791:Enzyme Inhibitors; D053495:Osteopontin; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium