Mesenchymal stem cells and cancer stem cells promote colorectal cancer cell growth and biological functions via cell-cell indirect contact

Abstract

Background: The effect of Mesenchymal Stem Cells (MSCs) on colorectal cancer stem cells (CCSCs) remains unclear. This study investigates the regulatory effects and mechanisms of human umbilical cord mesenchymal stem cells (huc-MSCs) on the biological functions of CCSCs.

Methods: The effects of huc-MSCs isolated from human umbilical cord tissues on CRC proliferation, apoptosis, the cell cycle, and CRC migration are investigated. The effect of CRC cell-huc-MSC interactions on angiogenesis is examined by analyzing pro- and anti-angiogenic factors. CSC-like sphere cells are used to examine the effects of MSCs on CCSC stemness. The influence of huc-MSCs on CCSC invasion is evaluated.

Results: Proteins associated with epithelial-mesenchymal transition (EMT) are detected, as are the activation of protein kinase B (AKT) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) in CCSCs. Treatment with huc-MSCs increases CRC cell migration and proliferation. After co-culture with huc-MSCs, CRC cells express higher levels of pro-angiogenic factors and enhanced tube formation compared with controls. In addition, CCSC-huc-MSC co-culture induces PI3K/Akt pathway activation, increases their stem cell characteristics, upregulates EMT, and promotes invasion.

Conclusions: CCSC-huc-MSC interactions enhance tumorigenesis via PI3K/AKT pathway activation, suggesting a novel CRC treatment target and providing insights into MSCs’ functions in the TME.

Graphical abstract:

Supplementary Information: The online version contains supplementary material available at 10.1186/s12935-025-03993-7.

Keywords: Cancer stem cell; Cell–cell indirect contact; Colorectal cancer; Huc-MSCs; PI3K/AKT pathway.