A new therapeutic target to prevent tumor growth

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  • Expression of specific proteins, gremlin 1 and meflin by cancer-associated fibroblasts (CAF), has the effect of promoting or slowing the development of colorectal cancer.

Colorectal cancer (colon and rectum) is the third most common cancer in men and second in women, accounting for about 12% of all cancer deaths in France, especially in people over 65. It is characterized by the presence of one or more tumors that develop from cells that represent the inner lining of the colon and rectum.

In a study published in the journal GastrointestinalResearchers at Nagoya University (Japan) may have devised a strategy to slow tumor progression: artificially changing the balance between carcinogenic fibroblasts and anti-cancer fibroblasts.

Major role of fibroblast

When cancer cells appear in the body, they are not isolated, but merge with healthy cells. Thanks to molecular exchanges, cancer cells “wake up” fibroblasts, especially those in neighboring tissues. Highly abundant, these support cells found in connective tissue are involved in the progression of colorectal cancer. Previous studies have shown that fibroblasts present in cancer tissues called cancer-associated fibroblasts (CAF) can be divided into at least two categories: those that promote cancer progression and those that slow it.

According to the authors of the study, interfering with the function of carcinogenic CAF can prevent cancer progression. They were therefore interested in bone morphogenetic proteins (BMPs). Secreted by stromal cells, they are associated with cancer progression when found in cancerous tissue in the colon.

Contains two proteins

To find out whether carcinogenic CAFs are involved in BMPs in the progression of colorectal cancer, researchers first identified genes associated with BMPs that are specifically expressed in colorectal CAFs. Two types of proteins, called meflin and gremlin 1, are encoded by such genes.

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By studying the role of these proteins in the progression of colorectal cancer in patients, the researchers found that people with high expression of meflin have favorable prognosis, whereas those with high expression of gramlin 1 have an adverse prognosis.

Further experiments in mice have shown that proliferation of colorectal cancer cells can be suppressed by the administration of a neutralizing antibody to overexpression of gremlin 1 or meflin.

“We hypothese that CAFs by Gremlin promote cancer progression by reducing BMP signaling, while CAFs by meeflin inhibit cancer growth by increasing BMP signaling”Says, the study’s co-author Prof. Etushi Anomoto. Accelerating stromal BMP signaling by either neutralizing an antibody neutralizing gremlin 1 or overexpressing meflin may be an interesting therapeutic strategy for the treatment of colorectal cancer, he said.




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