Autocrine secretion of a colorectum-derived growth factor by HT-29 human colon carcinoma cell line.
The human colon cancer cell line HT-29 produces a growth factor (CRDGF; Mr = 25,000) which inhibits EGF binding to a wide variety of different normal and tumoral cell types in culture. Scatchard analysis of EGF binding shows that CRDGF induces a decrease in EGF receptor affinity. In contrast, EGF binding to any of the human colorectal cancer cell lines tested, i.e., HT-29, HT-29 (clone D4), HRT-18 or CAL-14, remains unaltered in the presence of exogenous CRDGF. However, the inhibitory effect of CRDGF becomes apparent on HT-29 cells after overnight exposure of these to suramin (at 37 degrees C). A short exposure to suramin (1 hr at 4 degrees C) or a mild acid washing of HT-29 cells can partially restore the inhibitory activity of CRDGF. These observations suggest that the action of suramin results in an unmasking of substantial levels of CRDGF receptors on HT-29 cells. Scatchard analysis of EGF binding on suramin-treated HT-29 cells shows that CRDGF inhibits EGF binding by decreasing EGF receptor affinity, as previously observed with the non-colonic cell types. A similar unmasking of CRDGF receptors is observed when the other colorectal cell lines are exposed to suramin. These results provide evidence for a model in which the colorectal cell lines have the property of secreting a unique growth factor that binds to its receptor by an autocrine mechanism.
Culouscou
J M
JM
Laboratoire d'Immunopathologie, Faculté de Médecine, Marseilles, France.
Garrouste
F
F
Remacle-Bonnet
M
M
Bettetini
D
D
Marvaldi
J
J
Pommier
G
G
D002277:Carcinoma / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D013498:Suramin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D013498:Suramin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors