Researchers identify a promising target for treating chemo-resistant cancer cells

As medical professionals and scientists work to design new therapies for cancer, they come across a range of difficulties. One of the difficulties is intratumor heterogeneity—that is, the presence of various kinds of cancer cells inside the same tumor.

Cancer Cells

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Most often, these “mosaic” tumors comprise cells, like polypoidal giant cancer cells, that have progressed to become aggressive and resistant to radiation and chemotherapy.

Earlier, scientists have largely ignored polypoidal giant cancer cells (PGCCs) because studies had shown that these cells do not undergo mitosis, which refers to the mechanism usually needed for cell division.

But new studies have identified that PGCCs undergo amitotic budding—that is, cell division that does not take place through mitosis—and that their cell structure allows them to spread quickly.

Now, a study performed by a research team from Brown University had shed more light and found a promising target for treating these aggressive cancer cells. The researchers have recently published their findings in the Proceedings of the National Academy of Sciences.

PGCCs particularly depend on cell filaments, known as vimentin, for their migration. While vimentin is present in cells across the body, PGCCs were observed to have a higher proportion of vimentin when compared to non-PGCC control cells, and their vimentin was relatively more uniformly distributed across 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.”

Michelle Dawson, Study Author and Assistant Professor of Molecular Pharmacology, Physiology and Biotechnology, Brown University

When cells replicate inside a tumor, they become more and more crowded, and the adjacent cells tend to press closely against them. Ultimately, the cells crowd jointly in a solid-like mass. Vimentin imparts a more flexible, elastic structure to PGCCs, and this structure guards them against damage during this condition and enables them to squeeze past their adjacent cells to reach new and less crowded regions.

Therefore, when the team disrupted vimentin, they significantly decreased the cells’ capacity to move. Vimentin also seems to play a crucial role in reorganizing the nucleus of a dividing cell, and hence the disruption of vimentin may also help inhibit PGCCs from forming daughter cells.

As a subsequent step, Dawson and her collaborators are hoping to identify a biomarker for PGCCs, so that these cells can be studied in human tumors.

This study shows vimentin is overexpressed in PGCCs and is likely responsible for several of their abnormal behaviors. 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.”

Michelle Dawson, Study Author and Assistant Professor of Molecular Pharmacology, Physiology and Biotechnology, Brown University

Source:
Journal reference:

Xuan, B., et al. (2020) Vimentin filaments drive migratory persistence in polyploidal cancer cells. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2011912117.

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