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‐β 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. Int. J. Cancer 73:885–890, 1997. © 1997 Wiley‐Liss, Inc.