Cancerous Immunoglobulins and Ca215: Implications in Cancer Immunology

Abstract

Immunoglobulins are typically expressed by B cells in our normal immune system. However, certain normal human tissues, such as hyperplastic epithelial cells, cells of the immunologically privileged sites and the majority of cancer cells, have also been found to be sites of immunoglobulin production. Current research is lacking in regards to the differential immunoglobulin expression, the underling mechanisms of action and the biological implications of these cancerous immunoglobulins in cancer immunology. This article reviews the etiology of atypical immunoglobulin expression in normal non-B cells and cancer cells, with emphasis on the exploration of the possible mechanisms of action and biological function of these atypical immunoglobulins, by means of specific biological probes. In contrast to immunoglobulins of B cell origins, atypical immunoglobulins were found to carry additional post-translational modifications, including a unique carbohydrateassociated epitope recognized by RP215 monoclonal antibody. This unique RP215-specific epitope enables us to differentiate between these two types of immunoglobulins. Atypical immunoglobulins expressed by cancer cells have been a common subject of interest in cancer immunology. Furthermore, the recent accumulation of experimental evidence has indicated that these atypical immunoglobulins are essential for the growth and proliferation of cancer cells under our normal immune environment. RP215 monoclonal antibody also reacts with many other cancer cell-expressed glycoproteins, known as CA215, on the cancer cell surface. Apoptosis of cultured cancer cells can be induced and growth inhibition of implanted tumors can be observed in nude mouse animal models. Therefore, humanized RP215 monoclonal antibody, which reacts mainly with surface bound CA215, may have the potential to be developed as an anti-cancer drug for the treatment of human cancers. A better understanding of cancer cell-expressed immunoglobulins not only improves our knowledge of cancer immunology, but also benefits cancer patients in the field of cancer monitoring and therapeutic treatments.

Roles of antigen receptors and CA215 in the innate immunity of cancer cells

“…A variety of cancer cells and cancer cell lines have been shown to express functionally active TLRs, such as TLR-2, -3, -4, and -5 in ovarian cancer [29,61,62], TLR-3, -4, -5, and -9 in cervical cancer [61,[63][64][65], TLR-9 in lung cancer [43], TLR-4, -5, -9 in gastric cancer [66], and TLR-2, -3, and -4 in colorectal cancer cells lines [67]. In general, TLR-4 and TLR-9 was found to be most strongly expressed in human cancer cells [32]. However, the endogenous ligand for these cancerous TLRs and the mechanism by which TLRs promote carcinogenesis remains unknown [60].…”

“…During the past decade, distinct regulatory mechanisms for the expression of immunoglobulins in cancer cells compared to those of B cells have been demonstrated at the transcriptional, translational and posttranslational levels (14,32 [14]. Furthermore, only limited sets of predominant functional V H DJ H gene recombinations were identified in human cancer cells.…”

“…In a previous review, immunoglobulin expressions in many cancer cell lines and tissues were summarized [32]. With no exceptions, immunoglobulins can be detected in almost all types of cancer cells and cancerous tissues.…”

“…Three separate reviews have been published during the last five years regarding the research progress and up-todate knowledge of cancerous immunoglobulins [30][31][32]. Due to the lack of sufficient experimental evidence, the majority of these reviews only reported the summary of available research results with little definite conclusion regarding the roles and mechanisms of action of these cancerous immunoglobulins.…”

Dual Differential Roles of Cancerous Immunoglobulins as Suggested by Interactions with Human Serum Proteins

“…This observation may indicate the differences in the molecular nature between CA215 and cIgG. However, a few of these proteins listed in Table 3 are related to pro-cancer or anti-cancer properties to cancer cells [65][66][67][68][69][70][71][72][73][74]. The molecular nature and functions of these captured human serum proteins remain to be explored in the future [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68].…”