Secreted Frizzled Related Protein 4 (SFRP4) Modulates Cell Proliferation by Promoting Migration in Colon Cancer Tumorigenesis In Vitro

Abstract

Background Colon cancer (CC) is one of the most common cancers diagnosed in the United States. Despite the decline of overall incidences, the number of early-onset colon cancer (EOCC, [age < 50]) cases continues to rise at an alarming rate. EOCC tends to have more aggressive features, often diagnosed at a more advanced stage, and is associated with a poorer prognosis. Previous genomic studies identify EOCC as a unique disease with specific differentially expressed genes compared to late-onset colon cancer (LOCC). Secreted Frizzle Related Protein 4 (SFRP4) was significantly overexpressed in EOCC (p < 0.01, log2 fold change 3.97) and correlated with poor survival (p < 0.05) as well as increased tumor aggression. However, the role of SFRP4 of CC tumorigenesis, especially in those younger than 50 years, is not well understood. Therefore, the aim of this study was to evaluate the role of SFRP4 in CC tumorigenesis by modulating SFRP4 levels in vitro and determine how it affects proliferation and migration.Methods Cell lines were profiled for SFRP4 to choose an appropriate in vitro model to evaluate the role SFRP4 on CC tumorigenesis. A single cell line, Caco-2 (low SFRP4 expression), was chosen for proliferation and migration studies in vitro. Results Cell proliferation was decreased in Caco-2 cells upon treatment with human recombinant SFRP4 (rhSFRP) after 72 h (p <0.001). Transwell migration assay revealed significant increase in motility of Caco-2 cells after 24 h upon treatment with SFRP4. Conclusion Overexpression of SFRP4 modulates proliferation by promoting migration in Caco-2 cells, likely inducing epithelial-mesenchymal transition, which increases metastatic potential.