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Collagen Lose Accelerates Cancer Development

Collagen is the most abundant protein in the human body, which is produced by fibroblasts and exists in bones, tendons, and skin. During the occurrence and development of cancer, collagen tends to accumulate in and around tumors. Therefore, some researchers speculate that collagen helps to promote tumor growth, metastasis, or drug resistance.

 

Pancreatic cancer is a malignant tumor of the digestive tract that is difficult to diagnose and treat, which has many subtypes, 90% of which are pancreatic ductal adenocarcinoma (PDAC).

 

In recent years, the incidence and mortality of pancreatic cancer have increased significantly. The early diagnosis rate of pancreatic cancer is not high, which is often at an advanced stage when discovered. The 5-year survival rate is less than 7%, which is one of the most prognostic malignant tumors.

 

Type I collagen is the main component of the tumor matrix/microenvironment associated with PDAC, but the specific role and mechanism of collagen in the development of pancreatic cancer are still unclear.

 

On March 4, 2021, researchers from the University of Texas MD Anderson Cancer Center published a research paper entitled Type I collagen deletion in αSMA+ myofibroblasts augments immune suppression and accelerates the progression of pancreatic cancer in the Cancer Cell, indicating that the lack of expression of type I collagen in myofibroblasts can reduce the level of type I collagen in the pancreatic cancer tumor microenvironment, which will accelerate the progression of pancreatic cancer and enhance its immunosuppression.

 

Specifically, the loss of type I collagen can increase the expression of chemokine CXCL5 in cancer cells through SOX9, and the increase of CXCL5 leads to the recruitment of myeloid suppressor cells (MDSCs), which in turn inhibits the anti-tumor immune response. Blocking chemokine signal transduction can reverse the anti-tumor immune properties caused by the loss of type 1 collagen and slow down the progression of pancreatic cancer.

 

These findings indicate that collagen does not promote the development of cancer as previously thought, but is part of the human body’s cancer defense strategy, which plays a role in the tumor microenvironment and inhibits the progression of pancreatic cancer. A deeper understanding of the role of collagen in the tumor microenvironment will help enhance the body’s cancer defense capabilities to produce better effects of cancer defense and treatment.

 

To confirm the role of collagen in cancer development, the research team constructed a mouse model that the gene expressing collagen was deleted from myofibroblasts, and the total collagen in the tumor microenvironment reduced by more than 50%.

 

With the decrease of collagen, the growth of pancreatic cancer accelerated, and the overall survival rate of mice decreased significantly, indicating that collagen plays an important role in preventing cancer progression.

 

The research team further discovered that in tumors with reduced collagen, cancer cells produce higher levels of chemokines, which attract MDSCs, a type of immune cells that suppress the anti-tumor immune response. In tumors with reduced collagen, there are more MDSCs, and fewer T cells and B cells.

 

The use of targeted therapy to block the signal transduction activity of chemokines can reverse the anti-tumor immune properties of these tumors, slow the tumor progression, and restore it to a level similar to that of the control group.

As one of the most aggressive malignant tumors, pancreatic cancer has an immunosuppressive tumor microenvironment with poor immune detection.

 

The human body does its best to inhibit cancer development, and collagen is part of the break, which will produce a more harmful immunosuppressive tumor microenvironment when lost. Therefore, increasing collagen or enhancing its downstream pathways may be a strategy to slow the development of pancreatic cancer.

 

Overall, these findings indicate that collagen does not promote cancer development as previously thought, but is part of the human cancer defense strategy, which plays a role in the tumor microenvironment and inhibits the progression of pancreatic cancer. A deeper understanding of the role of collagen in the tumor microenvironment will help enhance the body’s cancer defense capabilities to produce better cancer defense and treatment effects.

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