A Novel Anticancer Effect of Thalidomide: Inhibition of Intercellular Adhesion Molecule-1–Mediated Cell Invasion and Metastasis through Suppression of Nuclear Factor-κB

Abstract

Purpose: Thalidomide has been reported to have antiangiogenic and antimetastatic effects.Intercellular adhesion molecule-1 (ICAM-1) was shown to be involved in monocyte adherence to epithelial cells and cancer cell invasion. In this study, we further investigated the role of ICAM-1 in tumorigenesis, including tumor formation and metastasis. ICAM-1 as a molecular target for cancer and the anticancer effect of thalidomide were investigated. Experimental Design: Expression of ICAM-1 protein in human lung cancer specimens was assessed by immunohistochemistry. ICAM-1 overexpressing A549 cells (A549/ICAM-1) were established to investigate the direct effect of ICAM-1 on in vitro cell invasion and in vivo tumor metastasis. Transient transfection and luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation were done to assess the activity and binding of nuclear factor-nB to the ICAM-1 promoter. A xenograft model in nude mice was conducted to evaluate the anticancer effect of thalidomide. Results: High expression of ICAM-1 in human lung cancer specimens was correlated with a greater risk of advanced cancers (stages III and IV). A549/ICAM-1 cells were shown to induce in vitro cell invasion and in vivo tumor metastasis. Anti-ICAM-1 antibody and thalidomide had inhibitory effect on these events. Thalidomide also suppressed tumor necrosis factor-a^induced ICAM-1 expression through inhibition of nuclear factor-nB binding to the ICAM-1 promoter. The in vivo xenograft model showed the effectiveness of thalidomide on tumor formation. Conclusion: These studies provide a framework for targeting ICAM-1 as a biologically based therapy for cancer, and thalidomide might be effective in human lung cancer.

Association Between Statin Use After Diagnosis of Esophageal Cancer and Survival: A Population-Based Cohort Study

“…Our findings are consistent with experimental studies which have demonstrated that statins promote apoptosis and limit proliferation in EAC cell lines [5][6][7][8] 6 , an adhesion molecule involved in trans-endothelial tumour cell migration and metastatic spread 23,24 . Whether these mechanisms operate to explain the associations observed in this study is not clear.…”

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

“…36 It has been reported that the expression of VEGF and/or ICAM-1 is correlated to the malignancy, or metastatic potential of tumors including osteosarcoma. 37,38 In our study, the mRNA levels of VEGF and ICAM-1 were significantly decreased by transfection of NF-kB decoy ODN, indicating that the metastatic potential of LM8 cells was decreased by the transfection of NF-kB decoy ODN.…”

The antitumor activity of an anti‐CD54 antibody in SCID mice xenografted with human breast, prostate, non‐small cell lung, and pancreatic tumor cell lines

“…Indeed, thalidomide, which also acts on CD54 is used in myeloma patients and has efficacy in lung tumors xenografted in mice. 55 Furthermore, many cancer patients are already immunosuppressed from their disease. Therefore, the predicted immunosuppressive activity of UV3 does not preclude its testing in Phase I clinical trials, where immunosuppression and other side effects are best determined during a dose escalation.…”