Cell-cell signaling by direct contact increases cell proliferation via a PI3K-dependent signal.
We report a novel mechanism of cellular growth control. Increasing the density of endothelial or smooth muscle cells in culture increased cell-cell contact and decreased cell spreading, leading to growth arrest. Using a new method to independently control cell-cell contact and cell spreading, we found that introducing cell-cell contact positively regulates proliferation, but that contact-mediated proliferation can be masked by changes in cell spreading: Round cells with many contacts proliferated less than spread cells with none. Physically blocking cell-cell contact or inhibiting PI3K signaling abrogated cell-cell induced proliferation, but inhibiting diffusible paracrine signaling did not. Thus, direct cell-cell contact induces proliferation in these cells.
Nelson
Celeste M
CM
Department of Biomedical Engineering, Johns Hopkins School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Chen
Christopher S
CS
D000818:Animals; D001973:Bromodeoxyuridine; D002417:Cattle; D002448:Cell Adhesion; D002450:Cell Communication / Q000502:physiology*; D002452:Cell Count; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D048429:Cell Size; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007365:Intercellular Junctions / Q000201:enzymology*; D007476:Ionophores / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology; D019899:Paracrine Communication / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
D004791:Enzyme Inhibitors; D007476:Ionophores; D011500:Protein Synthesis Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D001973:Bromodeoxyuridine