Ovarian cancer antigen CA 125 influences adhesion of human and mammalian cell lines in vitro.

Despite the widespread use of CA 125 for diagnostic and therapeutic evaluation of ovarian cancer function, the molecular nature of CA 125 is only poorly understood. It has been shown that CA 125 enhances the invasiveness of a benign endometriotic cell line in vitro. The invasiveness of cells is controlled by proteolytic activity, cell motility and cell adhesion. Therefore, we determined the influence of CA 125 on the cell adhesion of human carcinoma cell lines in vitro. In all tested human and mammalian cell lines (HECIA, AN3-CA, RL95-2, SK-OV-3, OAW-42, PA-1, HeLa, MCF7, T-47D, A-673, RT112, EJ28, EEC 145, CHO, MDBK, MDCK. LLC-PK1) the cell adhesion in vitro was significantly impaired by CA 125 in a time-dependent manner. Treatment of cells with trypsin diminished the effect of CA 125 on cell adhesion for two hours. By inhibition of protein synthesis with cycloheximide (2 microg/ml) the influence of trypsin on the anti-adhesive effect of CA 125 was significantly prolonged. The results suggest that the ovarian cancer antigen CA 125 influences cell adhesion in vitro.

Ovarian cancer antigen CA 125 enhances the invasiveness of the endometriotic cell line EEC 145.

OBJECTIVE: Ovarian cancer antigen CA 125 is used widely for diagnostic and therapeutic evaluation of ovarian cancer. Although the initial description of CA 125 was in 1981, its function is still unknown. In collagen gel system the invasiveness of the endometriotic cell line EEC 145 is enhanced by a proteinaceous factor in peritoneal fluid mimicking molecular features of CA 125. Therefore we hypothesize that this factor is CA 125. METHODS: The influence of heat-treated peritoneal fluid on the invasiveness of the endometriotic cell line EEC 145 and several human carcinoma cell lines (EJ28, RT112, AN3 CA, RL95-2, HEC-1-A, HeLa, MCF7, T-47D, and SK-OV-3) was investigated in a collagen gel invasion assay by addition of (1); 10% heat-treated peritoneal fluid, (2); peritoneal fluid after immunoprecipitation with antibodies directed to CA 125, and (3); purified CA 125. RESULTS: The invasion index of the endometriotic cell line EEC 145 significantly increased from 4.78 +/- 0.98 to 6.57 +/- 1.58 (P = .0001) by addition of 10% heat-treated peritoneal fluid to the culture medium. The invasion-promoting effect of peritoneal fluid was abolished by reduction of the CA 125 concentration through immunoprecipitation and was mimicked in a dose-dependent manner by addition of CA 125 to the culture medium. The invasiveness of the investigated human carcinoma cell lines was not affected by heat-treated peritoneal fluid of CA 125. CONCLUSION: The results are consistent with the hypothesis that CA 125 can influence invasiveness in a benign endometriotic cell line.

M-cadherin-mediated cell adhesion and complex formation with the catenins in myogenic mouse cells.

M-cadherin is a member of the multigene family of calcium-dependent intercellular adhesion molecules, the cadherins, which are involved in morphogenetic processes. Amino acid comparisons between M-cadherin and E-, N-, and P-cadherin suggested that M-cadherin diverged phylogenetically very early from these classical cadherins. It has been shown that M-cadherin is expressed in prenatal and adult skeletal muscle. In the cerebellum, M-cadherin is present in an adherens-type junction which differs in its molecular composition from the E-cadherin-mediated adherens-type junctions. These and other findings raised the question of whether M-cadherin and the classical cadherins share basic biochemical properties, notably the calcium-dependent resistance to proteolysis, mediation of calcium-dependent intercellular adhesion, and the capability to form M-cadherin complexes with the catenins. Here we show that M-cadherin is resistant to trypsin digestion in the presence of calcium ions but at lower trypsin concentrations than E-cadherin. When ectopically expressed in LMTK- cells, M-cadherin mediated calcium-dependent cell aggregation. Finally, M-cadherin was capable of forming two distinct cytoplasmic complexes in myogenic cells, either with alpha-catenin/beta-catenin or with alpha-catenin/plakoglobin, as E-and N-cadherin, for example, have previously been shown to form. The relative amount of these complexes changed during differentiation from C2C12 myoblasts to myotubes, although the molecular composition of each complex was unaffected during differentiation. These results demonstrate that M-cadherin shares important features with the classical cadherins despite its phylogenetic divergence.