Раковая наука и терапия

Similar Gene Regulation Patterns for Growth Inhibition of Cancer Cells by RP215 or Anti-Antigen Receptors

Abstract

Yiting Tang, Hao Zhang and Gregory Lee

RP215 is a monoclonal antibody generated against a carbohydrate-associated epitope of glycoproteins designated as CA215, which consists mainly of immunoglobulin superfamily proteins expressed by cancer cells including antigen receptors such as immunoglobulins and T-cell receptors. Since RP215 was shown to induce apoptosis and inhibit tumor growth in nude mouse models, the effects of RP215 and antibodies against antigen receptors on the gene regulations of cultured OC-3-VGH ovarian and C-33A cervical cancer cells were investigated through semi-quantitative RT-PCR. For both cell lines, RP215 and anti-antigen receptors were found to regulate similarly and consistently a number of genes including NFκB-1, IgG, P21, Cyclin D1, ribosomal P1 and c-fos with only exceptions for EGFR and ribosomal P0. Among toll-like receptor genes (TLR-2, -3, -4, -6, -7 and -9), differential levels of gene expressions in different cancer cell lines were observed. RP215 and anti-antigen receptors were found to up-regulate TLR-2 and/or TLR-3, whereas those of TLR-4 and TLR-9 were down regulated for both cancer cells. Based on these preliminary observations, it can be proposed that apoptosis of the two cancer cell lines was induced similarly by RP215 and anti-antigen receptors through consistent regulations of the same groups of genes. The innate immunity of cancer cells can also be affected by any of these antibodies through unidirectional regulations of certain toll-like receptors. Excellent correlations were obtained (R2=0.90-0.94) in terms of gene regulation patterns affected by any of these binding ligands. Therefore, the anti-cancer therapy of RP215 Mab may be, in part related to the surface bound antigen receptors and/or toll-like receptors in the innate immunity system, all of which may be involved in the growth and survival of cancer cells.