The role of human melanoma cell ICAM-1 expression on lymphokine activated killer cell-mediated lysis, and the effect of retinoic acid

Abstract

Intercellular adhesion molecule (ICAM-1) exists as a membrane-associated form (mICAM-1) on the surface of tumour cells as well as a soluble form (sICAM-1). This study analyses the ability of all- trans retinoic acid (RA) to alter both sICAM and mICAM-1 expression in C8161 and Hs294T human melanoma cell lines and investigates the involvement of ICAM-1 in the interaction between tumour and lymphokine-activated killer (LAK) cells using the Cr-51 release assay. Our data showed that 4-day pretreatment of the tumour cells with 10 −7 M RA and 10 −6 M RA induced an increase in lysis of both cell lines and also increased mICAM-1 expression without having any effect on sICAM-1 levels. Addition of blocking ICAM-1 antibody (10 μg ml −1 ) to the C8161 cells at an effector:tumour cell ratio of 40:1 caused a 2.3-fold reduction in lysis of tumour cells and a 3-fold reduction in lysis of RA-treated cells. Blocking ICAM-1 antibody at optimum concentrations of 5 μg ml −1 reduced lysis 1.8-fold in control Hs294T cells and 1.3-fold in RA-treated cells. Blocking the HLA–ABC complex had no effect on lysis. The more highly metastatic C8161 cells were found to secrete 4-fold greater levels of sICAM-1 than the poorly metastatic Hs294T cells and addition of sICAM-1 to the assay failed to affect lysis of either cell line but did induce a 2-fold decrease in lysis of RA-treated C8161 cells. Collectively, these data provide further evidence for ICAM-1 involvement in the tumour/LAK cell response and indicates that the RA-induced increase in mICAM-1 levels are partly responsible for the increase in susceptibility of the tumour cells. sICAM-1 appears to be unimportant in evasion of the tumour cells from LAK cell lysis, but may play a role in evasion of RA-treated C8161 cells. © 1999 Cancer Research Campaign

Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid

“…Retinoic acid treatment rendered hepatoma cell more susceptible to NK cells and also augmented the ability of hepatoma cells to induce IFNγ production from NK cells. It was previously reported that retinoic acid can modulate expression of HLA Class I, ICAM‐1 and CD95 in certain cell types and thereby affect their susceptibility to effector cell‐mediated cytolysis and apoptotic cell death 26, 28. This is not likely to be the case with hepatoma cells, however, because ATRA treatment did not affect the expression of these molecules on Huh7, HepG2 and Hep3B hepatoma cells (Fig.…”

Suppression of Natural Killer Cell Function and Production of Soluble ICAM‐1: Endometrial Stroma Versus Melanoma

“…metastasis. 10 This somewhat conflicting statement is explained by the existence of sICAM-1 that can interact with LFA-1 on the lymphocyte and block the lymphocyte from interacting with, and lysing the tumor cells. 11 -14 Nude mouse models have previously shown melanoma cells to be a source of sICAM-1, a finding supported by the observation that melanoma cell lines secrete sICAM-1.…”

“…In contrast, other groups were not able to confirm these findings. 10 However, the general opinion is that, in the in 6i6o situation, sICAM-1 may exist bound to other proteins or as a multimeric form which may have a great potential to bind to LFA-1 sites on the lymphocyte, thus contributing to tumor cell evasion.…”

“…In this context, it is interesting to consider that these tumor cells may evade cell lysis by shedding a soluble form of intercellular adhesion molecule-1 (sICAM-1). 10 The membrane form of ICAM-1 (mICAM-1) is crucial for the interaction with the immune system by binding to lymphocyte function-associated antigen (LFA)-1 on lymphoid cells. In contrast, the binding of sICAM-1 to the LFA-1 receptor could prevent the lymphocyte from interacting with mICAM-1 and thus prevent cell lysis occurring.…”

“…In contrast, the binding of sICAM-1 to the LFA-1 receptor could prevent the lymphocyte from interacting with mICAM-1 and thus prevent cell lysis occurring. 10 Indeed, several studies have shown a causal relationship between release of sICAM-1 by different cellular systems and inhibition of ICAM-1/ LFA-1-mediated cell adhesion and lysis. 11 -14 To gain insight into the potential relevance of the mechanisms thought to be implicated in immune escape by the endometrium, we compared two properties involved in this phenomenon: the ability to inhibit natural-killer (NK) cell-mediated activity and to secrete sICAM-1, between endometrial and melanoma cells.…”