Antibody targeting of C1q and its receptors (gC1qR and cC1qR) to inhibit tumor proliferation in human cancers 3943

Abstract Description Tumor proliferation is not only dependent on the accumulation of genetic mutations in cancer cells, but also supported by its local tumor microenvironment (TME), allowing for survival and migration in a supportive niche. Within the TME, deposition of complement proteins has been demonstrated to play dichotomous roles as both a tumor promoting and inhibiting agent. In particular, the complement protein C1q has been reported to be locally synthesized by the tumor cell, enhancing tumor cell adhesion, migration, and proliferation, as well as angiogenesis and metastasis. In addition, cancer cells have also been known to overexpress C1q and its receptors, gC1qR and cC1qR, on its surface as well as secrete gC1qR into the TME as a mechanism of immune evasion. However, contrasting evidence has also shown that C1q may induce apoptosis in certain cancers, like prostate and ovarian cancer, suggesting its role is context-dependent within the TME. Given the critical connection between complement and cancer, this study investigates the role of antibodies targeting the C1q-gC1qR axis on tumor proliferation. Expression of C1q and its associated receptors was examined in a panel of human cancers including neuroblastoma, lung, prostate, colorectal, and pancreatic cancers utilizing immunoassays such as western blots and ELISA screens. MTT cell proliferation assays were performed to assess the efficacy of complement targeting antibodies against tumor proliferation. Topic Categories Immune Mechanisms of Human Disease (HUM)