Research: Proteins that bind cancer cells to surrounding tissue slow their spread

2022-05-10 0 By

Surgical removal or chemotherapy may prove effective in eliminating the initial tumor, but often the cancer cells can break away and create secondary growth around the body.This is called metastatic cancer and is actually the leading cause of death of the disease, prompting a lot of research into ways to stop the spread.Now, a new study has identified a new target — a protein that stops cancer cells from migrating by sticking them to surrounding tissue.While the risks of metastatic cancer are well known, what is less clear is why some patients develop metastatic cancer after treatment for their primary tumor and others do not.Lingering cancer cells can migrate through the blood or lymphatic vessels to other parts of the body to form new tumors, and the authors of the new study are trying to learn more about and possibly intervene in this process with a protein called MFSD1.The team, made up of scientists from the Austrian Institute of Science and Technology and the University of Zurich, previously found the protein plays a role in cell migration in experiments with fruit flies.Fruit flies are one of the most commonly used models for biomedical research because of their short life cycle and the fact that they share many genes and biological functions with humans.The latest study focused on mice, where scientists engineered cancer cells that lacked the protein.This did make cancer cells move faster than those with the protein and showed that MFSD1 plays a preventive role in cell migration.The team observed the effect in live mice with breast, colon and skin cancers.”Metastasis increased strongly in the absence of MFSD1,” notes study author Daria Siekhaus.To find out why, the scientists conducted a stress test on cancer cells with and without MFSD1.This involved using a tiny rubber tool to scrape cells off the surface of a petri dish, and those containing MFSD1 quickly died due to mechanical stress.Those without the protein, however, remained largely intact, leading the team to conclude that mfSD1-deficient cells could more easily enter and pass through the blood.”We wanted to know why lower MFSD1 levels were beneficial to tumors in addition to allowing them to move more freely,” said Marko Roblek, lead author of the study.When cancer cells travel through the blood, for example, they experience a lot of mechanical stress.”By looking, the team found that MFSD1 exerts these effects by maintaining receptors on the cell surface called integrins, which allow cells to stick to each other as well as to a dense surrounding network called the extracellular matrix.Therefore, mfSD1-deficient tumor cells are less likely to recycle certain types of integrins.”As a result,” Siekhaus says, “cells become less attached to surrounding tissues and to each other, making them more likely to migrate.”While the experiments were conducted in mice, the team also explored MFSD1’s role in humans by examining data from cancer patients.This showed a correlation between levels of the protein and the outcome of the subjects.”We have seen that patients with certain forms of breast, stomach and lung cancer who have low levels of MFSD1 have a worse prognosis,” Roblek said.High levels of MFSD1 appear to be protective — it acts as an inhibitor of tumor metastasis.”The team’s findings lay the groundwork for a new form of treatment targeting MFSD1, potentially boosting its levels to curb the spread of metastatic cancer.Interestingly, the scientists also point out that if they can identify the gene that encodes the MFSD1 protein, then it could guide treatment by revealing how aggressive cancer is likely to be.”If this marker becomes more definitive, doctors could use it to help classify the aggressiveness of cancer and decide on different treatment options,” Siekhaus said.