Study discovers potential target for treating aggressive cancer cells

New research by a team at Brown University finds that special filaments called vimentin may be key to the spread of some aggressive, chemo-resistant cancer cells.

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.”

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).

This news story was authored by contributing science writer Kerry Benson.

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/Public Release. The material in this public release comes from the originating organization and may be of a point-in-time nature, edited for clarity, style and length. View in full here.

Study discovers potential target for treating aggressive cancer cells

New research by a team at Brown University finds that special filaments called vimentin may be key to the spread of some aggressive, chemo-resistant cancer cells.

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.”

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).

This news story was authored by contributing science writer Kerry Benson.

A study led by researchers at the Brown University School of Public Health found that using tuned LED lighting cut in half the number of sleep disturbances among older residents in long-term care.

Read Article

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With a focus on nursing home deaths after Hurricane Irma in 2017, study finds the effects of natural and other disasters on long-term care populations are vastly underestimated.

Read Article

Open details for When disasters strike, nursing home residents face considerable risk

A prominent global voice on COVID-19 and the new dean of the Brown University School of Public Health, Dr. Jha weighs in on lessons from the pandemic and how educators can best train future leaders in health and medicine.

Read Article

Open details for Dr. Ashish Jha: For public health leaders, ‘expertise plus humanity’ is key to success

/Public Release. The material in this public release comes from the originating organization and may be of a point-in-time nature, edited for clarity, style and length. View in full here.