A new tool developed by scientists at The Methodist Hospital separates tumor-causing cancer cells from more benign cells by subjecting the cells to a microscopic game of Plinko -- except only the squishiest cells make it through.
As reported in this week's Proceedings of the National Academy of Sciences (early edition online), the more flexible, tumor-causing cells navigated a gamut of tiny barriers, whereas the more rigid, more benign cells had trouble squeezing through 7 micrometer holes. Methodist scientists worked with University of Texas MD Anderson Cancer Center researchers to test the device with different kinds of cancer cells.
The work supports the hypothesis that cell squishiness indicates tumor potential. Most normal cells contain a developed cytoskeleton -- a network of tiny but strong rod-shaped proteins that give cells their shape and structure. In their feverish drive to divide, cancer cells may be diverting resources away from developing a cytoskeleton in favor of division, hence the squishiness.
"We have created many pathways for cells to cross barriers," said Methodist nanomedical faculty Lidong Qin, Ph.D., the project's principal investigator. "The throughput of a MS-Chip is at the level of one million cells. When a stiff cell blocks one particular barrier, many other bypasses will allow flexible cells to flow through."
Cancer stem cells are known to be squishier than other cancer cells. The team of scientists showed that flexible cells separated by the MS-Chip exhibited gene expression patterns consistent with cancer stem cells.
"Many papers indicate the presence of cancer stem cells means a worse prognosis for patients," said cancer scientist Jenny Chang, M.D., co-principal investigator and director of Methodist's Cancer Center. "Yet they are not typically quantified by doctors."
Subsequent analysis of separated cells by the Methodist and MD Anderson team showed the flexible cells were less likely to express cell cytoskeleton genes and more likely to express the motility genes that could contribute to metastasis.
By testing for the presence of metastatic cells, doctors may be able to tell whether cancer treatment was successful, or an as-yet untreated cancer's likelihood of metastasizing to another part of the body.