chondroitin and Peritoneal-Neoplasms

Primary peritoneal carcinosarcomas are similar to ovarian carcinomas in that they can metastasize by intraperitoneal dissemination; therefore, invasion of the submesothelial interstitial (stromal) matrix is an integral part of the pathology. Our objective was to study cell-matrix interactions that may influence invasive behavior of a novel, primary peritoneal carcinosarcoma cell line (PC880), and to assess how these cell-matrix interactions are different from frequently studied cultured ovarian carcinoma cells NIH:OVCAR-3, SKOV-3, and ES-2. We also wanted to determine how the expression of the cell-cell adhesion molecule E-cadherin is related to invasive behavior.. The PC880 cell line was established from ascites fluid of a patient diagnosed with primary peritoneal carcinosarcoma. Adhesion assays were done in titer plates coated with individual matrix components. Cell migration in monolayer cultures was assessed by the scratch wound assay method. Invasion assays were done using a three-dimensional type I collagen gel. Cytokeratin, vimentin, and E-cadherin were detected by Western blotting. E-cadherin mRNA was detected by RT-PCR.. PC880 cells adhered well to fibronectin, laminin, and vitronectin in an integrin-dependent manner. The cells also adhered to type I collagen and invaded a three-dimensional type I collagen matrix. The invasiveness of the PC880 cells was moderated by pretreatment of the collagen matrix with heparin or chondroitin sulfate (82 and 63% of control invasiveness, respectively), indicating a role of cell surface proteoglycans in promoting invasive phenotype. Treatment of PC880 cells with sodium chlorate also decreased invasiveness (80% of control), further confirming the role of cell surface proteoglycans. Treatment of PC880 cells with function-blocking antibody to alpha2 integrin decreased invasiveness (57% of control), indicating the role of integrins in promoting the invasive phenotype. The protease inhibitors GM6001, E-64, and AEBSF decreased invasiveness (35, 57, and 37% of control, respectively) of PC880 cells. The ES-2 cells also adhered to type I collagen, and invaded the three-dimensional type I collagen matrix; however, inhibitors such as heparin, chondroitin sulfate, function-blocking antibody to alpha2 integrin, E-64, and AEBSF were less effective in moderating the invasiveness. Inhibition of invasiveness with sodium chlorate was the same as in PC880 cell, while GM6001 did not inhibit invasiveness at all. The NIH:OVCAR-3 and SK-OV-3 cells were previously found to adhere to type I collagen, but these cells did not invade the three-dimensional type I collagen matrix. In a monolayer culture PC880 and ES-2 cells had significantly higher motility than NIH:OVCAR-3 and SK-OV-3 cells. Only these noninvasive cell lines expressed E-cadherin protein or mRNA.. PC880 is the first cell line established from primary peritoneal carcinosarcoma, and the cytoskeletal composition indicated that these cells represent the sarcomatous elements of the tumor. PC880 cells, similar to ES-2 cells, adhered to type I collagen, and invaded a three-dimensional collagen matrix. The invasion of the interstitial matrix by both the peritoneal carcinosarcoma and the ovarian carcinoma cell line was mediated by cell surface proteoglycans, alpha2 integrin, and proteases. The invasive cell behavior of PC880 and ES-2 cells correlated with a high degree of motility, and with the lack of expression of the cell-cell adhesion molecule E-cadherin.

Topics: Animals; Cadherins; Carcinosarcoma; Cell Adhesion; Cell Adhesion Molecules; Cell Movement; Chondroitin; Collagen Type I; Endopeptidases; Extracellular Matrix; Female; Fibronectins; Heparin; Humans; Integrin alpha2; Laminin; Middle Aged; Neoplasm Invasiveness; Ovarian Neoplasms; Peritoneal Neoplasms; Protease Inhibitors; Rats; RNA, Messenger; Tumor Cells, Cultured; Vitronectin

The effect of various glycosidases on the growth of solid hypotetraploid Ehrlich ascites tumour was investigated. The purified bacterial chondroitinase-ABC significantly inhibited the growth of tumour; chondroitinase-AC inhibited the tumour to some extent but chondro-4-sulphatase, chondro-6-sulphatase, streptomyces hyaluronidase, and β-glucuronidase had no inhibitory effect. Heat-treated chondroitinase-ABC had no inhibitory effect on the tumour growth. The growth of tumour cells which were injected subcutaneously after in vitro incubation with chondroitinase-ABC or -AC solution was decreased when compared with that of sham-treated cells.The injection of 1 ml of chondroitin sulphate A and chondroitin sulphate C solution prior to tumour inoculation into the same site promoted the tumour growth, while growth-stimulating effect of chondroitin sulphate B was ambiguous. The chondroitin sulphate appears to serve as a growth supporter which protects the surface of tumour cells and promotes the physiological surface function of the cells.

Topics: Animals; Carcinoma, Ehrlich Tumor; Chondroitin; Glucuronidase; Hyaluronoglucosaminidase; Lyases; Male; Mice; Peritoneal Neoplasms; Sulfates