Nature Cancer Blocks Tumor Signals To Stop Cancer Spread

June 2, 2020 /
BiovalleyBIOON / - For most people who die of cancer, the initial spread of thetumoris to blame"Transfer is the cause of most cancer patients," said Serge Fuchs, a professor at the University of Pennsylvania's School of Veterinary Medicine"However, there are not many drugs specifically targeting the transfer processIn a paper published in the journal Nature Cancer,, Fuchs worked with researchers from elsewhere to study the molecular mechanisms that promote the spread of cancer and to identify strategies to stop itUsing inhibitors of enzymes called p38 alpha kinases, they succeeded in reducing the metastasis ofmelanomamouse models, significantly prolonging survival"It seems to me that this treatment can be combined with surgical treatmentor other cancer treatments to remove the originaltumor,"Fuchs said "
study was based on years of research and collaboration by Ellen Pure of the University of Pennsylvania School of Veterinary Medicine, Constantinos Koumenis, Sandra Ryeom and Ben Stanger of the Perelman School of Medicine, and Dmitry Gabrilovich of the nearby Wistar Institute All the research has focused on different aspects of cancer biology image source: https://cn.bing.com
most of these discussions revolve around tumor-derived factors (TDF): various proteins, lipids, vesicles, genetic substances, signaling molecules, and other compounds that, in some cases, spread in the body Many of these factors, the scientists believe, help to "prepare for the growth of cancer soil," commonly known as "preparation for the growth of metastatic tumors," which makes certain areas of normal tissue more suitable for tumor cell growth, while tumor cells also move in the body and spread to these areas "We've been saying how tumors and tumor
factors are different, how their chemical properties are different, how their receptors are different, and how different types of normal cells perceive them," Fuchs said But in general, these areas of the lungs cause malignant cells to spread and promote their growth because they are the same as metastatic tumors "
to study exactly what causes metastasis, the researchers initially looked for elements that distinguished melanoma tumor cells, which tend edged more cells than less metastatic melanoma When they introduced TDF from more invasive tumor into normal mice, the animals formed a pre-metastasis microenvironment: a region conducive to cancer metastasis Animals that obtained TDF from less malignant melanoma barely developed these microenvironments they also noticed p38 because it is thought to be a response to certain factors secreted by cancer cells They observed that its activation was associated with metastasis, with higher levels of TDF activation by highly metastatic melanoma and lower activation by low metastatic melanoma to prove that the enzyme is important during the transfer process, the team tried two strategies: either to remove the enzyme by genetic manipulation, or to use an inhibitor to stop the activity of the kinase and stop its activation "Through both methods, we didn't get the microenvironment before the transfer," Fuchs said to provide a clinical context for their findings, they looked at white blood cells in patients melanoma The level of p38 activation in patients with no signs of metastasis was significantly lower than in those who were diagnosed with metastatic disease next, they examined the lungs of mice using TDF from a metastatic tumor source to learn more about how p38 nurtures premetal microenvironment The team found that TDF activating p38 in pulmonary fibroblasts (connective tissue cells) increases the activity of fibroblasts and stimulates the production of fibroblast-activated proteins (FAPs) FAP is a molecule that has long been of concern to Pur?and has been shown to affect the growth and metastasis of tumor The production of FAP helps to raise immune cells called neutrophils, which further act in the pre-transfer microenvironment of the lung tissue, enhancing their ability to capture and stimulate the growth of transfer cells to prevent the formation of this microenvironment and, ideally, to prevent metastasis, Fuchs and his colleagues treated the mice with two different p38 inhibitors, while surgically removing the original tumor the mice Both treatments inhibit the spread of cancer to the lungs and prolong the animal's survival one of the therapies they tested was ralimetinib, an experimental cancer drug that performed poorly in treating primary tumors But preliminary tests have shown that it is relatively safe, suggesting that it may be a special munition in the anti-cancer arsenal, inhibiting the proto
tumor diffusion (BioValleyBioon.com) References: Blocking signal s tags can's cancer's spread
Jun Gui gui al, p38 alpha-stress-aeid protein kinase drives of the formation of the pre-metastatic niche in the , Nature Cancer (2020) DOI: 10.1038/s43018-020-0064-0