A rat model to study the role of STn antigen in colon cancer.
Expression of the mucin-associated sialyl-Tn (STn) antigen has been associated with a decreased survival in patients with colorectal, gastric, and ovarian cancer. To better understand the role of STn antigen in tumor biology, we developed STn(+) (called LP) and STn(-) (called LN) clonal cell lines from a parental metastatic rat colon carcinoma cell line (LMCR). Both derivative cell lines exhibited identical proliferation rates in vitro. LP cells strongly expressed STn antigen both in vitro and in vivo, and were poorly tumorigenic when given to syngeneic rats. LN cells did not express STn antigen in vitro, but as in vivo tumors these cells rapidly acquired STn expression, readily formed tumors, and were highly lethal. When rats were given an otherwise lethal inoculum of i.p. LN cells, pre-immunization with synthetic STn antigen conjugated to keyhole limpet hemocyanin (STn-KLH) resulted in a 60% survival rate. When LN cells were injected subcutaneously in the presence of STn-KLH-sensitized lymphocytes, tumor growth was decreased. Distribution of STn antigen in normal organs of host rats is quite similar to that of humans. This model mimics human disease and should facilitate studies of mucin-associated antigens in tumor biology and the development of immunotherapeutic agents based on mucin-related antigens.
Ogata
S
S
Gastrointestinal Research Laboratory, Department of Medicine, Mount Sinai School of Medicine, NY, NY 10029, USA.
Ho
I
I
Maklansky
J
J
Chen
A
A
Werther
J L
JL
Reddish
M
M
Longenecker
B M
BM
Sigurdson
E
E
Iishi
S
S
Zhang
J Y
JY
Itzkowitz
S H
SH
D000818:Animals; D000917:Antibody Formation; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D019496:Cancer Vaccines; D002455:Cell Division / Q000502:physiology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D006001:Glycoconjugates; D006433:Hemocyanins / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D007274:Injections, Intraperitoneal; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D015996:Survival Rate; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006001:Glycoconjugates; C040286:Tn antigen; C055491:sialosyl-Tn antigen; C099077:sialyl-Tn antigen-keyhole-limpet hemocyanin conjugate; D006433:Hemocyanins