Study discovers potential target for treating aggressive cancer cells

October 21, 2020

PROVIDENCE, R.I. [Brown University] -- As researchers and medical professionals work to develop new treatments for cancer, they face a variety of challenges. One is intratumor heterogeneity -- the presence of multiple kinds of cancer cells within the same tumor. Often, these "mosaic" tumors include cells, such as polyploidal giant cancer cells, that have evolved to become aggressive and resistant to chemotherapy and radiation.

In the past, polyploidal giant cancer cells (PGCCs) have been largely ignored because studies had found that they do not undergo mitosis, which is the mechanism that is typically required for cell division. However, recent studies have found that PGCCs undergo amitotic budding -- cell division that does not occur through mitosis -- and that their cell structure enables them to spread rapidly.

A new study, published this month by a team of Brown University scientists in Proceedings of the National Academy of Sciences, sheds more light and identifies a potential target for treating these aggressive cancer cells.

Specifically, PGCCs rely on cell filaments called vimentin in order to migrate. Vimentin is found in cells throughout the body, but PGCCs were found to have a greater amount of vimentin compared to non-PGCC control cells, and their vimentin was much more evenly distributed throughout the cell.

"These cells appear to play an active role in invasion and metastasis, so targeting their migratory persistence could limit their effects on cancer progression," said study author Michelle Dawson, an assistant professor of molecular pharmacology, physiology and biotechnology at Brown University.

As cells replicate within a tumor, they become increasingly crowded, and neighboring cells press tightly against them. Eventually, the cells become jammed together in a solid-like mass. Vimentin provides PGCCs with a more flexible, elastic structure, which helps protect them from damage in this situation and allows them to squeeze past their neighboring cells to escape to new, less crowded areas.

Thus, when the researchers disrupted vimentin, they dramatically reduced the cells' ability to move. In addition, vimentin appears to play an important role in rearranging the nucleus of a dividing cell, so vimentin disruption could also help prevent PGCCs from forming daughter cells.

As a next step, Dawson and her colleagues hope to find a biomarker for PGCCs so that they can study these cells in human tumors.

"This study shows vimentin is overexpressed in PGCCs and is likely responsible for several of their abnormal behaviors," Dawson said. "Vimentin is a ubiquitous protein, so targeting vimentin directly may not be an answer, but drugs that target vimentin interactions may be effective in limiting the effects of these cells."
-end-
In addition to Dawson, other Brown University authors on the study were Botai Xuan, Deepraj Ghosh, Joy Jiang and Rachelle Shao. The study was funded by the National Science Foundation (1825174) and the National Institutes of Health (P30 GM110750).

Brown University

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.