# Mast cells interact directly with colorectal cancer cells to promote epithelial-to-mesenchymal transition

## TL;DR

Mast cells interact with colorectal cancer cells to promote cancer progression by transferring biological materials and inducing cell changes.

## Contribution

This study is the first to show contact-dependent pro-tumorigenic effects of mast cells in CRC and the transfer of biological materials to cancer cells.

## Key findings

- Mast cells promote epithelial-to-mesenchymal transition in CRC cells through calcium- and contact-dependent mechanisms.
- Inhibiting LFA-1 and ICAM1 integrin binding reduces EMT-related marker expression in CRC cells.
- Mast cells transfer mRNA molecules and other biological materials to CRC cells.

## Abstract

Mast cells (MCs), a type of granulocytic immune cell, can be both pro- and anti-tumorigenic in colorectal cancer (CRC). We hypothesized that these contrasting findings may be in part due to differential interactions of MCs with CRC subtypes. BRAF mutant CRC uniquely contains intestinal secretory cell types. In this study, we demonstrated that MCs are enriched in BRAF mutant CRC, likely because they are recruited by factors released from cancer secretory cells. To investigate the functional consequences of MC-CRC cell interactions, we performed direct coculture experiments. We demonstrated that MCs promote epithelial-to-mesenchymal transition (EMT) in CRC cells in a calcium- and contact-dependent fashion. Furthermore, inhibiting LFA-1 and ICAM1 integrin binding reduced the coculture-induced EMT-related marker expression in CRC cells. The MC-CRC cell interaction facilitates the transfer of biological materials, including mRNA molecules, from MCs to CRC cells. This study is the first to report a contact-dependent, pro-tumorigenic role of MCs in CRC, as well as the transfer of molecules encoded by MCs to CRC cells. These findings enhance our comprehension of cell-cell communication between immune and cancer cells. Furthermore, this work suggests that targeting MC-CRC interactions, particularly through modulating integrin pathways, could offer new therapeutic strategies for aggressive CRC subtypes.