Colonic Tumor CEA, CSAp and MUC-1 Expression following Radioimmunotherapy or Chemotherapy

Abstract

Understanding the changes in tumor biology following cytotoxic therapy may lead to a better understanding of the properties of surviving tumor cell populations and to an improved ability to target and treat these cells. This report addressed the time-dependent dynamic alterations in the expression of three tumor-associated antigens: carcinoembryonic antigen (CEA), colon-specific antigen (CSAp) and mucin-1 (MUC-1) following chemotherapy with 5-fluorouracil (5-FU) or radioimmunotherapy (RAIT; ¹³¹I-labeled anti-CEA IgG) in human colonic tumor xenografts. Immunoassay results show that CEA and MUC-1 expression all increase rapidly after either 5-FU or RAIT. GW-39 tumors show a 2.7-fold increase in CEA expression after a maximum tolerated dose of RAIT, being highest after 21 days, while LS174T and HT-29 tumors maximally increase expression 8.3- and 2.6-fold on day 7 after RAIT, respectively. The change in LS174T is short-term, whereas the change in HT-29 is maintained for at least 4 weeks. Serum CEA levels in these tumor- bearing mice also increase in parallel to the changes observed in tumor. MUC-1 increases 2.5-fold by day 5–7 following RAIT in LS174T tumors and 6-fold by day 14 following RAIT in GW-39 tumors, with a corresponding increase in serum MUC-1. Dramatic increases in CSAp after RAIT were also demonstrated in GW-39 tissue by immunohistochemistry. Thus, these data indicate that the response of tumor cells to low-dose-rate radiation from RAIT or to chemotherapy is associated with an increase of CEA, MUC-1 and CSAp.