C3(H2O) as a marker of human malignancy

Michelle Elvington, Ph.D.

Project Summary:

Emerging evidence indicates that intracellular activation of the central complement component C3 is involved in cellular metabolism and cell survival, key processes in malignant transformation. I discovered that the hydrolyzed complement component C3, C3(H2O), is loaded into cells from the extracellular milieu and serves as a source of C3 for these intracellular pathways. I hypothesize that C3(H2O) is intimately involved in cancer cell transformation and survival by driving metabolic reprogramming. Thus, I propose that plasma C3(H2O) will serve as a biomarker for disease activity in human cancer. Previously, a quantifiable method to measure C3(H2O), not confounded by other complement activation products, was unavailable. I have recently developed and optimized an immunoassay to specifically quantify C3(H2O) in human biospecimens. This gives the unique opportunity to evaluate serum C3(H2O) levels in human cancer patients. The studies proposed here will utilize this assay to evaluate C3(H2O) as a biomarker for disease and cancer progression in patients with multiple myeloma, prostate and breast cancer. These studies have the potential to monitor disease activity in a novel and meaningful way.

One of the challenges with tracking cancer progression and response to treatment is lack of a suitable biomarker. We have developed an assay for an immune system protein that is associated with cell survival and proliferation (hallmarks of cancer). Our study is focused on determining if this protein can serve as a novel biomarker that could thus provide a significant impact on cancer patient’s care and quality of life.