Paracrine interactions between mesothelial and colon-carcinoma cells in a rat model.
This study used a co-culture system with Transwell tissue-culture inserts to investigate the role of primary cultures of rat peritoneal mesothelial cells on the proliferation of rat colon-carcinoma cells (CC531 cells). Mesothelial cells significantly inhibited the growth of CC531 cells, while, conversely, CC531 cells stimulated the growth of mesothelial cells. Receptor-binding studies demonstrated the presence of high-affinity IGF-I receptors on the mesothelial and CC531 cells. Both cell types also produced IGF-I, as measured by radioimmunoassay. IGF-I stimulated DNA synthesis in mesothelial cells, but had no effect on the growth of CC531 cells. In co-culture, it was found that IGF-I potentiated the inhibitory effect of mesothelial cells on CC531 cells. The effect of IGF-I on mesothelial-cell proliferation was additive to the stimulatory effect of CC531 cells. TGF-beta had no effect on the growth of the CC531 cells, suggesting that this growth (-inhibitory) factor is not involved in the inhibitory effect of mesothelial cells on CC531 cell growth. The study provides evidence for the existence of a paracrine loop between mesothelial and colon-carcinoma cells, giving more insight into the basic cellular mechanisms that may modulate the growth of intraperitoneal colon carcinoma. Inhibition of CC531-cell proliferation by rat mesothelial cells might explain the earlier finding that tumour cells grow poorly in a surgically uncompromised abdomen.
van der Wal
B C
BC
Department of Surgery, University Hospital, Rotterdam, The Netherlands.
Hofland
L J
LJ
Marquet
R L
RL
van Koetsveld
P M
PM
van Rossen
M E
ME
van Eijck
C H
CH
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D007633:Keratins / Q000032:analysis; D008297:Male; D019899:Paracrine Communication; D051381:Rats; D011919:Rats, Inbred Strains; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000032:analysis; D014841:von Willebrand Factor / Q000378:metabolism
D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D014746:Vimentin; D014841:von Willebrand Factor; D007334:Insulin-Like Growth Factor I; D007633:Keratins; D017526:Receptor, IGF Type 1