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Susceptibility of colorectal‐carcinoma cells to natural‐killer‐mediated lysis: Relationship to CEA expression and degree of differentiation
Author(s) -
Prado Ivete B.,
Laudanna Antonio A.,
Carneiro Célia R. W.
Publication year - 1995
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.2910610618
Subject(s) - sodium butyrate , natural killer cell , lysis , biology , cytotoxicity , cancer research , lymphokine activated killer cell , cell , immunology , cellular differentiation , cell culture , in vitro , interleukin 21 , immune system , t cell , gene , genetics
This study addresses the relevance of colorectal‐carcinoma‐cell (CRC) CEA expression and degree of differentiation in natural‐killer(NK)‐mediated lysis susceptibility. A 51 Cr‐release cytotoxicity assay performed with 5 human CRC lines demonstrated that CRC CEA expression was related to resistance to NK lysis. Moreover, the addition of anti‐CEA Fab fragments to the assay led to a significant increase of lysability of high‐CEA‐producing and NK‐resistant cells (LS 174‐T), whereas purified CEA drastically reduced lysis of low‐CEA‐producing and NK‐susceptible cells (LISP‐1) in a dose‐dependent manner. These results strongly suggest that CEA plays a causal role in CRC resistance to NK lysis. Nevertheless, our data did not demonstrate CEA binding to effector cell surface, suggesting that CEA expression can protect CRC, possibly by preventing NK‐tumor‐cell adhesion to occur. Our results also show that CRC susceptibility to NK lysis was related to a less differentiated phenotype. HCT‐8, which are poorly differentiated and low‐CEA‐producing cells, were cultured in vitro in the presence of the differentiation agent sodium butyrate. Treated cells became less susceptible to NK lysis as they progressed towards a more differentiated phenotype. However, CEA production was not altered upon differentiation. Our study thus demonstrates that both features, CEA expression and degree of cellular differentiation, may individually influence CRC susceptibility to NK lysis. © 1995 Wiley‐Liss, Inc .