A Transcriptomic Insight into the Impact of Colon Cancer Cells on Mast Cells

Abstract

Mast cells (MCs) are one of the first immune cells recruited to a tumor. It is well recognized that MCs accumulate in colon cancer lesion and their density is associated with the clinical outcomes. However, the molecular mechanism of how colon cancer cells may modify MC function is still unclear. In this study, primary human MCs were generated from CD34+ progenitor cells and a 3D coculture model was developed to study the interplay between colon cancer cells and MCs. By comparing the transcriptomic profile of colon cancer-cocultured MCs versus control MCs, we identified a number of deregulated genes, such as MMP-2, VEGF-A, PDGF-A, COX2, NOTCH1 and ISG15, which contribute to the enrichment of cancer-related pathways. Intriguingly, pre-stimulation with a TLR2 agonist prior to colon cancer coculture induced upregulation of multiple interferon-inducible genes as well as MHC molecules in MCs. Our study provides an alternative approach to study the influence of colon cancer on MCs. The transcriptome signature of colon cancer-cocultured MCs may potentially reflect the mechanism of how colon cancer cells educate MCs to become pro-tumorigenic in the initial phase and how a subsequent inflammatory signal—e.g., TLR2 ligands—may modify their responses in the cancer milieu.