Researchers have identified a gene that promotes the spread of cancer cells throughout the body
Sist anmeldt: 14.06.2024
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Metastatic cancer cells, which cause 90% of cancer-related deaths, must overcome many obstacles to spread from the primary tumor through the bloodstream and settle in various tissues.
A new study from researchers at the Massachusetts General Cancer Center has identified a gene whose expression confers a growth advantage on these cells.
Mechanistically speaking, gene expression allows metastatic cancer cells to induce changes in their environment so that they can grow in new locations in the body. The results were published in the journal Nature Cell Biology.
“Our findings point to potentially new therapeutic pathways to specifically target metastatic cancer,” said senior author Raoul Mostoslavsky, MD, PhD, who is the scientific director of the Kranz Family Cancer Research Center at Massachusetts General Cancer Center.
Mostoslavsky and colleagues first compared gene expression patterns in primary tumors and metastatic tumors in mice with pancreatic or breast cancer. After identifying different genes that were upregulated in metastatic tumors, the researchers individually suppressed each gene.
In these experiments, silencing the Gstt1 gene had no effect on primary tumor cells in mice, but it did deprive metastatic cancer cells of their ability to grow and spread. It also blocked cell growth in two human pancreatic cancer cell lines derived from metastases.
Gstt1 encodes an enzyme that is a member of a superfamily of proteins involved in protecting cells from toxins, among other functions. Mechanistic studies have shown that the enzyme Gstt1 causes metastatic cancer cells to modify and secrete a protein called fibronectin, which is important for attaching cells to the extracellular matrix, the large network of proteins and other molecules that surround, support and give structure to cells and tissues in the body. p>
"Gstt1 changes the matrix surrounding metastatic cells so they can grow in these foreign sites," Mostoslavsky said. "Our findings may lead to new strategies for treating metastatic disease. This would be particularly significant for pancreatic cancer, since most patients present with metastases at initial diagnosis."