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Cancer metastasis (metastasis) is the leading cause of cancer-related deaths
.
How to inhibit the metastasis of cancer cells to other parts and continue to grow has become an important goal in the development of cancer therapies
Recently, researchers from the German Cancer Research Center (DKFZ) and the Heidelberg University Medical School have brought a new result
.
They found that blood vessels can produce and release a growth factor that promotes the metastasis of cancer cells throughout the body
Blood vessels provide the nutrients needed for tumor growth and also provide a channel for cancer cells to spread throughout the body
.
Whether the tumor cells in the blood circulation can successfully "set up" in a new location and grow into a new tumor depends largely on the local environment
In this study, the scientists simulated the situation after surgical removal of tumor patients, and investigated the microenvironment where the “seeds” of cancer cells in the blood circulation are located when the primary tumors of the experimental mice have been surgically removed
.
Using endothelial cell transcriptomics and serum proteomics, the research team found that primary tumors induce inflammation throughout the body, systematically reprogramming the body's vascular endothelium, and preparing for the metastasis of cancer cells
.
In the presence of primary tumors, vascular endothelial cells will produce a large amount of a molecule called LRG1, that is, leucine-rich alpha-2 glycoprotein 1
In the lung metastasis model, LRG1 produced in large quantities by vascular endothelial cells in the lung stimulates the growth of nearby connective tissue cells, creating a microenvironment that promotes the growth of cancer cells, allowing cancer cells in the blood circulation to settle and grow here
.
When the tumor formed by these cancer cells grows to a certain size, the metastatic tumor will again promote the production of LRG1 like the primary tumor
▲In mice with tumor metastasis to the lung, tumor cells (blue) grow around blood vessels in the lungs (red) and invade normal lung tissue (green) (picture source: reference [2])
Through a meta-analysis of retrospective clinical studies, researchers found that the concentration of LRG1 in the serum of cancer patients also increased correspondingly, further supporting the association of LRG1 as a key molecule with cancer metastasis
.
Following this discovery, the researchers tried to block LRG1 to observe the effect on cancer metastasis
.
In two mouse models of spontaneous metastasis, the researchers used anti-LRG1 neutralizing antibodies to the mice after the primary tumor was surgically removed
Note: The original text has been deleted
Reference materials:
[1] Mahak Singhal et al.
[2] Blood vessels produce growth factor that promotes metastases.
