COLORECTAL-CARCINOMA INVASION INHIBITION BY CO17-1A GA733 ANTIGEN ANDITS MURINE HOMOLOG/

Background: The gastrointestinal carcinoma antigen GA733 is a potentia l target for passive and active immunotherapy for patients with colore ctal carcinoma, This antigen has been characterized previously as a he mophilic adhesion (i.e., adhesion to self) protein, but the functional consequences of homophilic adhesion for tumor growth and invasion are unknown, The availability of a murine homologue of GA733, i.e., murin e epithelial glycoprotein (mEGP), allows for functional analysis of ce ll adhesion as it relates to tumor growth and invasion, both in vitro and in vivo. Methods: CT-26 murine colorectal carcinoma cells were tra nsfected with complementary DNAs encoding either the human or the muri ne antigen. GA733- or mEGP-producing cells were evaluated for homophil ic adhesion, growth on plastic surfaces, colony formation in soft agar , and invasion through a reconstructed basement membrane (Matrigel). m EGP-producing cells were also examined for their capacity to metastasi ze in mice. Reported P values are two-sided. Results: Compared with co ntrol cells, mEGP-producing cells showed significantly lower growth ra tes, colony formation, and invasion through Matrigel in vitro (all P v alues <.05), Compared ,vith vector-only transfected cells and parental cells, mEGP-producing cells showed a reduction in metastatic potentia l in syngeneic immunodeficient and immunocompetent mice (dl P values < .05), In contrast to mEGP-transfected cells, GA733-transfected cells d id not exhibit significantly reduced growth or colony formation in vit ro (all P values >.05), However, GA733-transfected cells did show redu ced invasion through Matrigel compared with vector-only transfected ce lls or parental cells tall P values <.05), Conclusion: The adhesion pr oteins GA733 and mEGP inhibit invasion of tumor cells.