van der Wal B C, Hofland L J, Marquet R L, van Koetsveld P M, van Rossen M E, van Eijck C H
Department of Surgery, University Hospital, Rotterdam, The Netherlands.
Int J Cancer. 1997 Dec 10;73(6):885-90. doi: 10.1002/(sici)1097-0215(19971210)73:6<885::aid-ijc21>3.0.co;2-2.
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.
本研究采用带有Transwell组织培养小室的共培养系统，以研究大鼠腹膜间皮细胞原代培养物对大鼠结肠癌细胞（CC531细胞）增殖的作用。间皮细胞显著抑制CC531细胞的生长，而相反，CC531细胞刺激间皮细胞的生长。受体结合研究表明间皮细胞和CC531细胞上存在高亲和力的胰岛素样生长因子-I（IGF-I）受体。通过放射免疫测定法检测发现，两种细胞类型均产生IGF-I。IGF-I刺激间皮细胞中的DNA合成，但对CC531细胞的生长没有影响。在共培养中，发现IGF-I增强了间皮细胞对CC531细胞的抑制作用。IGF-I对间皮细胞增殖的作用与CC531细胞的刺激作用具有叠加性。转化生长因子-β（TGF-β）对CC531细胞的生长没有影响，这表明这种生长（抑制）因子不参与间皮细胞对CC531细胞生长的抑制作用。该研究为间皮细胞与结肠癌细胞之间旁分泌环的存在提供了证据，从而更深入地了解了可能调节腹膜内结肠癌生长的基本细胞机制。大鼠间皮细胞对CC531细胞增殖的抑制作用可能解释了早期的发现，即肿瘤细胞在手术未受影响的腹腔中生长不佳。
