Characterization of zinc-alpha(2)-glycoprotein as a cell adhesion moleculethat inhibits the proliferation of an oral tumor cell line

Zn-alpha(2)-glycoprotein (Zn alpha(2)gp) is a soluble protein widely distri buted in body fluids and glandular epithelia. We have found it to be expres sed in stratified epithelia as well. Zn alpha(2)gp is clinically correlated with differentiation in various epithelial tumors, including oral and epid ermal tumors. We have cloned epidermal Zn alpha(2)gp and report the prepara tion of the recombinant protein in a Baculovirus expression system. Like th e native molecule, recombinant Zn alpha(2)gp has RNase activity. Zn alpha(2 )gp functions as a matrix protein for the Tu-138 oral squamous cell carcino ma cell line. Cell attachment to Zn alpha(2)gp is comparable to that for fi bronectin and is inhibited by the synthetic RGD peptides RGD, RGDV, and RGD S. Attachment is also inhibited by the antibody to integrin alpha(5)beta(1) (the fibronectin receptor), but not by antibodies to integrins alpha(v)bet a(3), alpha(3)beta(1), and alpha(2)beta(1) We find that the proliferation o f Tu-138 cells is inhibited on a Zn alpha(2)gp matrix, as compared with oth er matrix proteins (fibronectin, vitronectin, laminin, and collagens I and IV) on which growth resembles that on the BSA control. We believe that the role of Zn alpha(2)gp in differentiation and its RNase activity are two lik ely suspects as agents of the inhibition of proliferation. (C) 1999 Wiley-L iss, Inc.