Colonic tumor CEA, CSAp and MUC-1 expression following radioimmunotherapy or chemotherapy.
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; (131)I-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.
Garden State Cancer Center, Belleville, NJ 07109, USA. dmodrak@gscancer.org
D E
DE
Modrak
D V
DV
Gold
D M
DM
Goldenberg
R D
RD
Blumenthal
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use; D001918:Brachytherapy; D002272:Carcinoembryonic Antigen / Q000276:immunology / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000628:therapy*; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D018396:Mucin-1 / Q000378:metabolism*; D009368:Neoplasm Transplantation; D013997:Time Factors; D014183:Transplantation, Heterologous
D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; D002272:Carcinoembryonic Antigen; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D018396:Mucin-1; C030139:colon-specific antigen; D005472:Fluorouracil