ICAM-1 increases in vitro adhesion and cytotoxicity in a murine fibrosarcoma.
Cellular adhesion and specific cytotoxicity are two essential components for the successful cellular therapy of cancer. Intercellular adhesion molecule-1 (ICAM-1) is an essential participant in lymphocyte-endothelial cell adhesion and may also play a role in lymphocyte-mediated cytotoxicity. To study the effect of ICAM-1 on adhesion and cytotoxicity in vitro, MCA-105 tumor cells were cotransfected with ICAM-1 and the gene for neomycin resistance (NeoR). Two clones (Clones 81 and 149) with confirmed enhancement of ICAM-1 expression were selected. Studies were performed examining adhesion of lymphocytes to HUVECs, MCA-105, Clone 81 or Clone 149 alone, or combinations of the three tumor cell lines with HUVECs. Peripheral blood lymphocytes labeled with 51Cr were used and adhesion was determined by counting in a gamma-counter after rinsing away nonadherent cells. Cytotoxicity was performed using 51Cr-labeled MCA-105, NeoR, Clone 81, and Clone 149 target cells. LAK cells cultured from splenocytes of normal mice were used as the effector cells and a chromium release assay was performed. Adhesion data showed significant increases in adhesion (P < 0.05) for Clones 81 and 149 compared to MCA-105. However, the combination of HUVECs and tumor cells to mimic the in vivo condition had a variable effect on adhesion compared to tumor cells alone. Cytotoxicity experiments demonstrated that Clone 149 was significantly (P < 0.05) more susceptible to lysis by normal LAK cells compared to MCA-105, NeoR, and Clone 81. These results suggest that increased ICAM-1 expression enhances the susceptibility of tumor cells to lysis by LAK cells.
Burno
D K
DK
Tumor Immunology Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Fabian
D F
DF
Lefor
A T
AT
D000818:Animals; D002448:Cell Adhesion; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D014162:Transfection
D018799:Intercellular Adhesion Molecule-1