Colorectal carcinoma invasion inhibition by CO17-1A/GA733 antigen and its murine homologue.
BACKGROUND
The gastrointestinal carcinoma antigen GA733 is a potential target for passive and active immunotherapy for patients with colorectal carcinoma. This antigen has been characterized previously as a homophilic 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., murine epithelial glycoprotein (mEGP), allows for functional analysis of cell adhesion as it relates to tumor growth and invasion, both in vitro and in vivo.


METHODS
CT-26 murine colorectal carcinoma cells were transfected with complementary DNAs encoding either the human or the murine antigen. GA733- or mEGP-producing cells were evaluated for homophilic adhesion, growth on plastic surfaces, colony formation in soft agar, and invasion through a reconstructed basement membrane (Matrigel). mEGP-producing cells were also examined for their capacity to metastasize in mice. Reported P values are two-sided.


RESULTS
Compared with control cells, mEGP-producing cells showed significantly lower growth rates, colony formation, and invasion through Matrigel in vitro (all P values <.05). Compared with vector-only transfected cells and parental cells, mEGP-producing cells showed a reduction in metastatic potential in syngeneic immunodeficient and immunocompetent mice (all P values <.05). In contrast to mEGP-transfected cells, GA733-transfected cells did not exhibit significantly reduced growth or colony formation in vitro (all P values >.05). However, GA733-transfected cells did show reduced invasion through Matrigel compared with vector-only transfected cells or parental cells (all P values <.05).


CONCLUSIONS
The adhesion proteins GA733 and mEGP inhibit invasion of tumor cells.
Basak
S
S
The Wistar Institute, Philadelphia, PA 19104, USA.
Speicher
D
D
Eck
S
S
Wunner
W
W
Maul
G
G
Simmons
M S
MS
Herlyn
D
D
D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000378:metabolism / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule