Investigation of escape mechanisms by tumor cells from the immunological defenses of the host was continued. The hypothesis proposed for immunoresistance in the strain nonspecific TA3-Ha and TA3-MM mammary carcinoma ascites cells, namely, masking of histocompatibility (H-2?a?) antigens at the cell surface by large mucin-like glycoprotein molecules (epiglycanin), is supported by antibody absorption studies and physicochemical and morphological results. Recent transplantation experiments performed in both syngeneic (A/WySn) and allogeneic (C57BL) recipients show no immunosuppressive activity by epiglycanin and are consistent with the masking hypothesis. For example, injection of the glycoprotein under various conditions prior to challenge by TA3-Ha ascites cells on day 7 had no detectable effect upon either the tumor growth rate or the time of death (due to tumor growth) of the animals. Antibody could be detected in both syngeneic and allogeneic mice 3 to 4 weeks following injection of TA3-Ha cells, and also in mice following repeated injections (i.p.) of epiglycanin with Freunds complete adjuvant. Several monoclonal antibodies to epiglycanin have been prepared in pure form. In two other immunoresistant cell lines, TA3-St/ticol/-A mouse mammary carcinoma and YACIR mouse lymphoma, large cell-surface glycoproteins were also demonstrated. These were not detected in the corresponding immunosensitive lines, TA3-St and YAC, respectively. No evidence has been obtained to implicate these glycoproteins in an antigen-masking mechanism. Studies on the characteristics of the tumor specific transplanation antigen at the surface of polyoma virus transformed cells revealed the possible involvement of the carbohydrate moiety in the antigenic determinant. (AG)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA018600-10
Application #
3164966
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1978-01-01
Project End
1986-06-30
Budget Start
1985-01-01
Budget End
1986-06-30
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
Watkins, S C; Slayter, H S; Codington, J F (1991) Intracellular pathway of a mucin-type membrane glycoprotein in mouse mammary tumor cells. Carbohydr Res 213:185-200
Beppu, M; Codington, J F; Lasky, R D et al. (1987) Epiglycanin-immunoreactive glycoproteins in mouse fetal tissues and fetal cells in culture. J Natl Cancer Inst 78:1169-75
Codington, J F; Deak, M R; Frim, D M et al. (1986) Evidence for the presence of an N-acetyllactosamine-type chain in epiglycanin. Arch Biochem Biophys 251:47-54
Schmit, A; Condington, J F; Slayter, H S (1986) Epiglycanin as a membrane glycoprotein. Isolation of plasma membrane from the TA3-Ha tumor cell. Carbohydr Res 151:173-84
Wold, J K; Slayter, H S; Codington, J F et al. (1985) Location of an epitopic site on epiglycanin by molecular immunoelectron microscopy. Biochem J 227:231-7
Walker-Nasir, E; Codington, J F; Lampert, L A et al. (1985) Effects of retinoic acid on ascites cells of the TA3 mouse mammary carcinoma. Experientia 41:402-4