[Cell Sub-Journal] New targets for pancreatic cancer microbiome and immune regulation!

This article is original from Translational Medicine Network, please indicate the source for reprinting 

Author: TMZHI

Introduction: Different from other solid tumors, the stromal component of pancreatic cancer accounts for more than 80% of the tumor volume, including abundant extracellular matrix, pancreatic stellate cells, and tumor-associated fibroblasts

On August 8, Anderson Cancer Center published a research article titled: "Oncogenic collagen I homotrimers from cancer cells bind to α3β1 integrin and impact tumor microbiome and immunity to promote pancreatic cancer" in "Cancer Cell", revealing that The Col1 homotrimer-α3β1 integrin signaling axis is a cancer-specific therapeutic target

Doi: 10.

Research Background

 01 

During the occurrence and development of pancreatic cancer, a matrix-rich and highly immunosuppressive microenvironment is formed by the interaction of tumor cells, immune cells, stromal cells and extracellular matrix.

Collagen type I (Col1), the most abundant protein in the human body, widely accumulates in the microenvironment of pancreatic ductal adenocarcinoma (PDAC), and is heterologous to normal collagen type I (Col1) produced by fibroblasts in the microenvironment Compared with trimers (α1/α2/α1), pancreatic cancer cells can specifically produce unique Col1 homotrimers (α1/α1/α1), however, the production of Col1 by pancreatic cancer cells has a negative impact on pancreatic cancer tumor biology.

Biological functions of Col1 homotrimers

 02 

The researchers constructed the spontaneous tumorigenic model mice of pancreatic cancer with the conditional knockout of Col1 homotrimer, and found that after knocking out the Col1 homotrimer, the survival of spontaneous pancreatic cancer mice was significantly prolonged, and the pancreatic tumor burden was significantly reduced.

 03 

Using transcriptomics, we found that Col1 homotrimers significantly up-regulated proliferation-related pathways such as glutathione metabolism, DNA replication, RNA splicing, and cell cycle, which were dependent on integrin α3β1 (Figure 2)

Figure 2.

Deletion of Col1 homotrimers

 04 

Using microbiome sequencing and intratumoral immune cell profiling, we found that loss of Col1 homotrimers preserved gut microbiota homeostasis in mice with pancreatic cancer (Fig.

Figure 3.

Significance

 05 

This study demonstrates that cancer cell-derived oncogenic Col1 homotrimers also influence the tumor immune microenvironment to promote immunosuppression, establishes that this immune regulation is associated with a unique intratumoral microbiome, and develops new tools that can be used in the microbiome and immune system.

References:

This article is intended to introduce the progress of medical research and cannot be used as a reference for treatment plans

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