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The high lysability by lak cells of colon‐carcinoma cells resistant to doxorubicin is associated with a high expression of ICAM‐1, LFA‐3, NCA and a less‐differentiated phenotype
Author(s) -
Rivoltini Licia,
Cattoretti Giorgio,
Arienti Flavio,
Mastroianni Antonio,
Melani Cecilia,
Colombo Mario P.,
Parmiani Giorgio
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910470521
Subject(s) - cytotoxic t cell , microbiology and biotechnology , biology , monoclonal antibody , cell adhesion molecule , retinoic acid , cell culture , cancer research , cell adhesion , in vitro , antibody , immunology , cell , biochemistry , genetics
Abstract A human colon‐carcinoma ceil subline resistant to doxorubicin (LoVo/Dx), previously shown to be more lysed than the chemosensitive subline LoVo/H by different immune effectors, is reported here to be similarly susceptible to direct, anti‐proliferative effect of soluble cytokines (TNF‐α and/or IFN‐γ). More adhesion molecules ICAM‐1, LFA‐3 and NCA were expressed on LoVo/Dx than on LoVo/H, while no significant amounts of CEA were detectable on the cell surface or in culture supernatant of either tumor subline. Anti‐ICAM‐1, anti‐LFA‐3 and anti‐NCA monoclonal antibodies (MAbs) caused a marked reduction of lysis by interleukin‐2 (IL‐2) activated lymphocytes (LAK) of LoVo/Dx, whereas a lower effect was evident on LoVo/H. A pool of these antibodies was able to further increase the inhibition of the LAK lysis of both sublines. LoVo/Dx displayed a less differentiated phenotype as assessed by morphology, in vitro growth and altered or increased expression of markers such as desmoplakin and vimentin respectively, and disappearance of mucin. Treatment of LoVo sublines with differentiating agents (dimethylformamide and retinoic acid) led to a decreased expression of all adhesion molecules studied, accompanied by increased resistance to LAK‐mediated lysis. These data indicate that sensitivity of chemoresistant tumor cells to cytotoxic effectors depends on the level of expression of adhesion molecules, including NCA, and is related to differentiation stage.