TY - JOUR
T1 - Cell-cell signaling by direct contact increases cell proliferation via a PI3K-dependent signal
AU - Nelson, Celeste M.
AU - Chen, Christopher S.
N1 - Funding Information:
This work was supported in part by the Whitaker Foundation, NIGMS (GM 60692), and DARPA. We thank John L. Tan, Joe Tien, Joe G.N. Garcia, and Lew Romer for helpful discussions. C.M.N. acknowledges financial support from the Whitaker Foundation.
PY - 2002/3/13
Y1 - 2002/3/13
N2 - 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.
AB - 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.
KW - Cell shape
KW - Extracellular matrix
KW - Intercellular adhesion
KW - Microcontact printing
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U2 - 10.1016/S0014-5793(02)02370-0
DO - 10.1016/S0014-5793(02)02370-0
M3 - Article
C2 - 11943158
AN - SCOPUS:0037070553
SN - 0014-5793
VL - 514
SP - 238
EP - 242
JO - FEBS Letters
JF - FEBS Letters
IS - 2-3
ER -