Undergraduate Researcher Stony Brook Univ., SUNY Copiague, New York, United States
Disclosure(s):
Jianna Carter: No financial relationships to disclose
Introduction/Rationale: Within the tumor microenvironment, C1q and its receptors (gC1qR and cC1qR) have been found to play both pro- and anti-tumorogenic roles. gC1qR secretion has been observed to act as a metastatic driver and play a role in tumor defense. The current study aims to understand the interactions of both membrane-localized and secreted C1q and C1qRs in the tumor microenvironment of colorectal cancer (CRC), as well as potential differences in these interactions between African American (AA) and Caucasian American (CA) cell lines.
Methods: Western Blot analysis revealed that both C1q and the C1qRs were expressed in all cell lines at both whole-cell and membrane levels, though the detection of C1q itself varied. This was performed alongside ELISA assays to quantitatively assess secretion of C1q and the C1qRs. gC1qR was demonstrated to be secreted into the extracellular environment by all four cell lines; C1q secretion was observed in small amounts. gC1qR secreted into the tumor microenvironment may compete with membrane-localized gC1qR for the binding of anti-gC1qR, potentially playing a protective role against immune-cell-expressed C1q. Cells from each line were treated with C1q, gC1qR, cC1qR, and the antibodies (𝛼) to each, and MTT assays were used to study cell viability and proliferation.
Results: Increased dose of C1q was found to promote tumor cell proliferation in CRC, likely favoring the overexpression of C1q by other cell types within the microenvironment for growth. Cell lines from CAs produced pro-proliferative responses when treated with C1q. AA cell lines demonstrated greater sensitivity to treatment with 𝛼C1q. This was further supported by a significant drop in viability attributed to the inhibition of the receptor cC1qR using 𝛼cC1qR.
Conclusion: These findings point towards C1q and C1qRs as potential therapeutic targets in CRCs, and more in-depth studies into the role of these components are ongoing to further understand the mechanism by which they act within the tumor microenvironment.