Collagenase-IV in human trophoblast invasion and differentiation

Trophoblast cells are unique with respect to their functions and responsibilities. These cells demonstrate three sequential phenotypes, proliferation and invasion into the endometrium, differentiation to form syncytia and endocrine secretions. Equipped with these properties placental trophoblasts are endowed with a variety of functions, like implantation of the blastocyst to the endometrium, providing nutrition to the developing embryo and also transmitting extraordinary array of signals for the embryonic development. Experimental evidences and logical extrapolation suggest that these functions are precisely controlled by growth factors, cytokines and hormones produced either by the trophoblast themselves or by the utero-placental unit. Any error in this control mechanism has extremely adverse consequences. The cells also synthesize a large number of enzymes, amongst which collagenase type IV secretion is involved in digestion of underlying basement membrane necessary for the process of invasion. Our results implicate the enzyme in the functional differentiation of the trophoblast as well. Inhibitors to this enzyme inhibit trophoblast differentiation as monitored by secretion of hCG and progesterone, the two markers of trophoblastic differentiation. In contrast, BeWo cells, a choriocarcinoma cell line which does not differentiate spontaneously, undergo increased proliferation when challenged with EGF. The results indicate the possibility of invasive and differentiative phenotypes to be coupled. Exact molecular involvements in this coupling process are looked into.