GELATINASE AND ONCOFETAL FIBRONECTIN SECRETION IS DEPENDENT ON INTEGRIN EXPRESSION ON HUMAN CYTOTROPHOBLASTS

Collagenolytic activity of cytotrophoblasts is stimulated by glycoproteins of the extracellular matrix and since this stimulation can possibly occur through integrins, we measured the gelatinolytic activity of villous and extravillous cytotrophoblasts according to the type of integrins expressed on these cells, Cytotrophoblasts were isolated from legal abortions, immunopurified with anti-CD45, separated according to their expression of histocompatibility-linked antigen (HLA)-G, alpha(6) or alpha(5) integrin subunits and cultured for 5 days on plastic or agarose. Fetal fibronectin, human chorionic gonadotrophin (HCG) and the gelatinolytic activity were measured in the culture supernatants, Following immunopurification with anti-CD45, the gelatinolytic activity of cytotrophoblasts was significantly higher than before, indicating that contaminating lymphomyeloid cells secreted gelatinolytic inhibitors. HLA-G positive cells secreted significantly more gelatinases than HLA-G negative cells but their HCG secretion was similar, Compared to alpha(5) positive cells, alpha(6) positive cytotrophoblasts secreted significantly more gelatinases, significantly less fibronectin but similar amounts of HCG, We conclude that during trophoblast invasion, extravillous cytotrophoblasts (HLA-G positive) expressing the alpha(6) integrin subunit represent the invasive population of cells (high gelatinase and low fibronectin secretion). When expression of the alpha(5) integrin subunit is turned on, their invasive behaviour ceases and they secrete low amounts of gelatinases and high concentrations of fibronectin.