Scientists analyze the impact of tumor microenvironment on tumor growth

Scientists analyze the impact of tumor microenvironment on tumor growth

Scientists analyze the impact of tumor microenvironment on tumor growth Scientists analyze the impact of tumor microenvironment on tumor growth

Picture produced by China Science News

Picture produced by China Science News

At 23:00, June 30, 2021, Beijing time, the German Cancer Research Center and the Michael Boutros group of Heidelberg University published a research paper entitled "Microenvironmental innate immune signaling and cell mechanical responses promote tumor growth" online in Developmental Cell magazine
.

Developmental Cell

The authors used tissue-specific CRISPR gene knockout technology to generate mutants of the BMP signaling pathway to establish 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

Dr.
Zhou Jun from the German Cancer Research Center is the first author and co-corresponding author of the paper.
The German Cancer Research Center and Professor Michael Boutros of Heidelberg University are the last corresponding authors of the paper
.

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

Tissue development also requires dynamic cell rearrangement, including competition and elimination of a cell population to expand a more competitive cell population

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

The growth of tumors also uses this mechanism to destroy surrounding cells in order to facilitate their own growth

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

Therefore, it is very important to study the mechanism of how tumors grow in dense tissues

Activation of innate immunity in the tumor microenvironment stimulates tumor growth

Activation of innate immunity in the tumor microenvironment stimulates tumor growth

The authors 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
.

At the same time, they found that the innate immune activation is mainly in the normal cells surrounding the tumor (tumor microenvironment)

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 (Figure 1)
.

The researchers then found that genetic deletion of NFkB activity and its upstream regulatory molecule PGRP-LA can reduce cell apoptosis in the tumor microenvironment and inhibit tumor growth

Figure 1.
The effect of innate immune system activation in the tumor microenvironment on tumor growth
.

Figure 1.
The effect of innate immune system activation in the tumor microenvironment on tumor growth
.

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

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
.

When tissue homeostasis is unbalanced, such as during tumor growth, the molecular mechanism of this competitive growth is not very clear

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

The administration of ROCK inhibitors can rescue the cellular mechanical response associated with tumors and cause the expression levels of stress, immunity and apoptosis related genes in the tumor’s intestine to decrease
.
In addition, ROCK inhibitor treatment can effectively limit tumor growth
.

Figure 2.
A model of inflammatory cell apoptosis caused by mechanical competition in the tumor microenvironment
.

Figure 2.
A model of inflammatory cell apoptosis caused by mechanical competition in the tumor microenvironment
.

In summary, the authors found that tumor cells use mechanical competitive pressure to squeeze out surrounding normal cells, thereby activating the NFkB pathway of immune response, inducing the separation and apoptosis of surrounding normal cells, thereby promoting tumor growth
.
This process requires activation of the ROCK/JNK signaling pathway related to mechanical force response by regulating the upstream peptidoglycan recognition protein PGRP-LA (Figure 2)
.

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
.
Another latest independent study in a human kidney epithelial cell model also found and confirmed that the NFkB pathway of immune response participates in the regulation of the infection process and uses mechanical stress to eliminate the immune protection mechanism of infected cells
.
(Source: Science Net)

Related paper information: https://doi.
org/10.
1016/j.
devcel.
2021.
06.
007

https://doi.
org/10.
1016/j.
devcel.
2021.
06.
007 https://doi.
org/10.
1016/j.
devcel.
2021.
06.
007