Growth regulation and co-stimulation of human colorectal cancer cell lines by insulin-like growth factor I, II and transforming growth factor alpha.
We have tested growth factor responsiveness of a panel of eight human colorectal carcinoma cell lines. Insulin-like growth factors I and II (IGF-I and IGF-II) stimulated growth of five lines (HT-29, LS411N, LS513, SW480, WiDr). At 30 ng ml-1 both factors enhanced growth up to 3-fold. They induced half-maximal stimulation at 1.9-6.51 ng ml-1. Even after delayed addition IGF-I and II significantly enhanced growth in a short-term proliferation assay. They exerted maximal effects under limiting serum conditions (0.5% FCS) and at low cell density (1.25-5 x 10(4) ml-1). Using these conditions transforming growth factor alpha (TGF alpha) enhanced proliferation of all IGF-responsive cell lines, except SW480. 1.11-3.31 ng ml-1 were required to obtain a half-maximal response. With 10-20 ng ml-1 maximal stimulation occurred at plateau values different from those for IGF-I/II. Proliferation of all cell lines responsive to both IGF-I and TGF alpha was further enhanced by combining both factors, resulting a synergistic response of LS513, while the effects on HT-29, LS411N and WiDr were additive. With HT-29 and LS411N a 24 h exposure to TGF alpha was sufficient to obtain a full response in the co-stimulatory assay. Our results illustrate the importance of IGF-I/II and TGF alpha as stimulators of growth of colorectal carcinomas.
Lahm
H
H
Swiss Institute for Experimental Cancer Research, Department of Cellular Biology, Epalinges.
Suardet
L
L
Laurent
P L
PL
Fischer
J R
JR
Ceyhan
A
A
Givel
J C
JC
Odartchenko
N
N
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D012709:Serum Albumin / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D012709:Serum Albumin; D016211:Transforming Growth Factor alpha; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II