Gregory Lee, Cheng-Yuan Huang, Hao Zhang and Yiting Tang
Relationships between the expressions of immunoglobulins by cancer cells and those of toll-like receptors were investigated through comparative gene regulation studies to understand their roles and mechanisms of action in cancer immunology. RP215 is a monoclonal antibody generated in 1987 and found to recognize the carbohydrate-associated epitope which is detected preferentially in the heavy chains of immunoglobulins expressed by cancer cells, but not in normal immune cells. In this report, RP215 was used to study interactions of cancerous immunoglobulins with toll-like receptors in the innate immunity of cancer cells. From gene regulation studies, with OC-3-VGH ovarian and C-33A cervical cancer cell lines, it was demonstrated that the expressions of cancerous toll-like receptors (TLR-2, -3, -4, -6, -7 and -9) are strongly influenced by the incubation of cancer cells with RP215 or antibodies against human IgG. For example, both RP215 and anti-human IgG were found in high correlation to up-regulate TLR-3 expressions by 2.5 and 3.5 fold, respectively, whereas those of TLR-4 and TLR-9 were downregulated by 50% to 80% of the untreated. Based on these studies, it is reasonable to postulate that cancerous immunoglobulins are highly involved to modulate the innate immunity of cancer cells to allow the growth/proliferation of cancer cells within the human body.
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