Dev Cell: Zhou Jun and others analyze the impact of tumor microenvironment on tumor growth

Tissue development is achieved through the adaptation of cells to the local environment

The dynamic interaction between different cell populations directly or indirectly promotes competition for limited resources and space within the organization

On June 30, 2021, the German Cancer Research Center and the Michael Boutros group of Heidelberg University published an online research paper titled: Microenvironmental innate immune signaling and cell mechanical responses promote tumor growth in the Journal of Developmental Cell

The study used tissue-specific CRISPR gene knockout technology to generate mutants of the BMP signaling pathway and established an inducible Drosophila intestinal tumor model to study the impact of tumor microenvironment on tumor growth

This study analyzed the molecular mechanisms of innate immune signaling pathways in the tumor microenvironment and the mechanical cell competition pressure formed by the tumor on the surrounding normal cells that affect tumor growth

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In the early stage of tumor growth, this mechanism of cell self-expansion plays a vital role in tumor growth and development

Activation of innate immunity in the tumor microenvironment stimulates tumor growth

The research team first analyzed the gene expression profiles of intestinal tumors and normal tissues and found that the expression levels of genes related to innate immune response in tumors have increased significantly

Further research found that the activation of the innate immune (NFκB) signaling pathway in the tumor-bearing intestine requires the upstream receptor PGRP-LA

At the same time, apoptotic cells can secrete the cytokine Unpaired (Upd) to activate the activity of the JAK/STAT signaling pathway in tumor cells to promote tumor growth

The effect of innate immune system activation in tumor microenvironment on tumor growth

Tumors use mechanical cells to compete for pressure to eliminate surrounding normal cells

Animals will eliminate some inappropriate cells during development to maintain their own tissue health

They found that tumor growth induces Rho-related protein kinase (ROCK)/JNK-related cellular mechanical response in its microenvironment

In general, the study found that tumor cells squeezed out the surrounding normal cells through mechanical competitive pressure, thereby activating the NFkB pathway of immune response, inducing the separation and apoptosis of surrounding normal cells, thereby promoting tumor growth

A model of inflammatory cell apoptosis induced by mechanical competition in the tumor microenvironment

This study clarified for the first time that a tumor “hijacks” an inflammatory feedback mechanism through mechanical cell competition to eliminate intestinal epithelial cells around the tumor, thereby supporting its own growth

Original source:

Jun Zhou, et al.