With a particular focus on the lung, the researchers performed global gene expression analyses of the metastatic niche. They discovered that in the presence of a primary tumor, the endothelial cells lining the interior of blood vessels produced the protein LRG1 (leucine-rich alpha-2-glycoprotein 1) in large quantities. “The blood vessels produced LRG1 exclusively in the presence of the primary tumor, which stimulates the growth of nearby connective tissue cells in the lung. This creates a tumor cell growth-promoting microenvironment (‘niche’) where circulating tumor cells can settle and grow into lung metastasis,” said DKFZ researcher Mahak Singhal, first author of the current study, adding, “This is the first time we have demonstrated that the metastasis-promoting effect of the niche is triggered over long distances by the primary tumor.” From a certain size, the metastases then act like a primary tumor themselves, again promoting the formation of LRG1.
How does the progression of metastasis change when the key molecule LRG1 is blocked with an antibody? In fact, scientists were able to slow the metastatic growth of breast and lung tumors in this way. One of the most surprising findings of the current study was that LRG1 was not only produced by blood vessels at the metastasis site, but that it was produced by endothelial cells throughout the body and released into the circulation. Thus, the researchers were even able to detect the metastasis-promoting molecule directly in blood samples. “We can now detect LRG1 produced by endothelial cells as a biomarker indicative of a metastatic tumor. In addition, we want to validate LRG1 as a target for new therapeutic approaches that may be able to halt the metastatic spread of tumors,” says study leader Hellmut Augustin, summarizing the current results.
Source: German Cancer Research Center
Source: Healthcare in Europe