Greiff Andrea H, Fischer William M, Sehgal Inder
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, USA.
Clin Exp Metastasis. 2002;19(8):727-33. doi: 10.1023/a:1021304700234.
Epithelial cancer cell invasion is facilitated by stromal cells, immune cells, endothelial cells and other epithelial cells. We have used two human papilloma immortalized prostate cell lines, CA-HPV-10 from a carcinoma and PZ-HPV-7 cells from normal prostatic epithelium to study cell-cell influences on growth, gelatinase secretion, invasion and responses to TGFbeta1. We found that co-culture with CA-10 carcinoma cells stimulates proliferation of the PZ-7 epithelial line. TGFbeta1 inhibited growth of both lines, but while inhibitory effects on the CA-10 cells diminished after removal of the peptide, inhibition of PZ-7 was lasting. Interestingly, the TGFbeta-induced growth inhibition in PZ-7 cells could be partially reversed by co-culture with CA-10 cells. Co-culture with CA cells in a 3-chamber invasion assay also promoted invasion of PZ cells. CA-10 invasion was enhanced by co-culture with TGFbeta1-treated-PZ-7 cultures and this enhancement was associated with TGFbeta1-induced secretion of matrix metalloproteinase-9. Our observations suggest that interaction between prostate cancer cells and prostate epithelial cells may promote proliferation of the epithelial cell population and produce a paracrine source of MMP-9 which may facilitate early cancer cell invasion.
基质细胞、免疫细胞、内皮细胞和其他上皮细胞可促进上皮癌细胞的侵袭。我们使用了两种人乳头瘤病毒永生化前列腺细胞系，一种来自癌组织的CA-HPV-10和来自正常前列腺上皮的PZ-HPV-7细胞，来研究细胞间对生长、明胶酶分泌、侵袭以及对TGFβ1反应的影响。我们发现，与CA-10癌细胞共培养可刺激PZ-7上皮细胞系的增殖。TGFβ1抑制这两种细胞系的生长，但去除该肽后，对CA-10细胞的抑制作用减弱，而对PZ-7细胞的抑制作用持续存在。有趣的是，与CA-10细胞共培养可部分逆转TGFβ对PZ-7细胞生长的抑制作用。在三室侵袭试验中与CA细胞共培养也可促进PZ细胞的侵袭。与经TGFβ1处理的PZ-7培养物共培养可增强CA-10的侵袭，这种增强与TGFβ1诱导的基质金属蛋白酶-9分泌有关。我们的观察结果表明，前列腺癌细胞与前列腺上皮细胞之间的相互作用可能促进上皮细胞群体的增殖，并产生旁分泌来源的MMP-9，这可能有助于癌细胞的早期侵袭。
