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Johns Hopkins Pediatric

Super-sized, Chemo-Resistant Cancer Cells



Some cancer cells basically thumb their nose at treatment. Other cells may succumb, but not these hardy survivors.

This situation, called cancer therapeutic resistance, is the vexing problem that challenges scientist Sarah Amend, Ph.D. With Ken Pienta, M.D., and colleagues, Amend has been conducting rigorous analysis of the cells that aren’t killed by chemotherapy.

In recent research, published in the journals Clinical and Experimental Metastasis and Neoplasia, “we found that the cells that survive cytotoxic chemotherapy enter a unique cell state,” says Amend.

Normally, all cells undergo cell division by the process of mitosis: a parent cell gives rise to two offspring cells. “We found that while cytotoxic chemotherapy kills cells that undergo mitosis, cells that survive the days and weeks after therapy exit the typical cell cycle and progress through multiple growth and DNA replication phases instead – without cell division!” This process, called endocycling, results in jumbo cells, she adds.

“The cells are dramatically larger – about 70-fold their normal size.”

The investigators discovered that these endocycling cancer cells gain a new power: “They have increased metastatic potential,” says Amend. Among other things, “we found that they also have increased directional movement and are highly deformable, thus enabling invasion.” Even more concerning is that these endocycling cancer cells “are impervious to subsequent treatment with additional chemotherapy drugs.”

However, they may have found a potential Achilles heel: a key protein called Vimentin, the culprit that enables these jumbo cells. “We found that destabilizing Vimentin reverses the motility phenotype.” The next step is to figure out how to disrupt this process. “These studies suggest that eliminating this cell state is critical for improving the success of cancer therapy.”

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