New therapeutic goal to prevent tumor progression

The third most common cancer in men and the second most common in women, Le Cancer Colorectal (Colon and rectum) About 12% of cancer deaths in France occur, especially among those over 65 years of age. It takes the form of one or more tumors developing from cells that line the inner lining of the colon and rectum.

In a study published in the journal Gastroenterology, University of Nagoya (Japan) researchers have found a strategy to slow tumor progression: artificially altering the balance between cancer-causing fibroblasts and anti-cancer fibroblasts.

The main role of fibroblasts

When cancer cells appear in the body, they do not separate but merge with healthy cells. Thanks to molecular conversion, cancer cells especially “wake up” Nearby tissues contain fibroblasts. Very abundantly, these helper cells found in connective tissue are involved in the progression of colorectal cancer. Previous studies have shown that cancerous tissue fibroblasts are called cancer-associated fibroblasts (CAFs), which can be divided into at least two groups: those that promote cancer progression and those that slow it down.

According to the study authors, interfering with the functioning of carcinogenic CAFs can inhibit the progression of cancer. Hence they were interested in bone morphogenetic proteins (BMP). Secreted by stromal cells, when found in cancerous tissue in the colon they are associated with cancer progression.

There are two proteins

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

By studying the role of these proteins in the progression of colorectal cancer in patients, the researchers found that those with high expression of meflin had a favorable prognosis, while those with high expression of gremlin 1 had an unfavorable prognosis.

Further experiments in mice have shown that the proliferation of colorectal cancer cells can be suppressed by the administration of an antibody that neutralizes Gremlin 1 or by increased circulation of meflin.

“We hyp hypothesized that CAFs by Gremlin 1 would promote cancer progression by reducing BMP signaling, while CAFs by Miflin could inhibit cancer growth by increasing BMP signaling”, Said co-author of the study, Professor Atsushi Enomoto. He said that exacerbating stromal BMP signaling by using an antibody that neutralizes Gremlin 1 or by over-expressing meflin would be an interesting treatment strategy to treat colorectal cancer.