TY - JOUR
T1 - A rat model to study the role of STn antigen in colon cancer
AU - Ogata, Shunichiro
AU - Ho, Immanuel
AU - Maklansky, Joseph
AU - Chen, Anli
AU - Werther, J. Lawrence
AU - Reddish, Mark
AU - Longenecker, B. Michael
AU - Sigurdson, Elin
AU - Iishi, Seichiro
AU - Zhang, Jie Yu
AU - Itzkowitz, Steven H.
N1 - Funding Information:
This work was supported in part by PHS grant RO1 CA52491 and CA81363 (SHI), The Peptic Ulcer and Gastric Cancer Research Foundation, and The Chemotherapy Foundation.
PY - 2001/11
Y1 - 2001/11
N2 - 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.
AB - 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.
KW - Colon cancer
KW - Immunotherapy
KW - Mucin
KW - Sialyl-Tn
UR - http://www.scopus.com/inward/record.url?scp=0035526298&partnerID=8YFLogxK
U2 - 10.1023/A:1022248408857
DO - 10.1023/A:1022248408857
M3 - Article
C2 - 12820721
AN - SCOPUS:0035526298
SN - 0282-0080
VL - 18
SP - 871
EP - 882
JO - Glycoconjugate Journal
JF - Glycoconjugate Journal
IS - 11-12
ER -