Capturing Cancer Cells With Rough Surfaces

Tumors often shed malignant cells that then travel through a person’s bloodstream. Because these cells can seed metastases, cancer researchers want ways of detecting these circulating tumor cells to understand and prevent cancer progression. In a new study, researchers report a cheap method for capturing these cells using just a rough glass slide (ACS Nano, DOI: 10.1021/nn304719q).

Because circulating tumor cells offer a noninvasive opportunity to study a cancer and assess a patient’s prognosis, the search for ways to detect them has exploded over the past five years, says Mehmet Toner, a bioengineer at Massachusetts General Hospital, who was not involved in this study. Unfortunately, these cells are rare, so it’s not easy to pull them out of the blood stream.

One method uses antibodies to home in on molecules on the cells’ surfaces. But antibodies are expensive and not all cancer cells express the antibodies’ targets on their surfaces, says Jianping Fu of the University of Michigan, Ann Arbor.

To develop an alternative method, Fu and his team wanted to exploit a feature common to most types of cancer cells. Other researchers have reported that cancer cells preferentially attach to rough surfaces over smooth ones. These groups have attached antibodies to textured surfaces to trap circulating cancer cells from blood samples. Fu and his colleagues thought they could toss out the expensive antibodies and grab cancer cells based solely on their preference for roughened surfaces.

The team scored the surfaces of glass slides using an inexpensive method called reactive ion etching, which bombards surfaces with charged ions. When the researchers pipetted breast, prostate, and cervical cancer cells to roughened glass slides and smooth ones, the team found that all cell types preferentially stuck to the etched ones.

To begin to compare the behavior of cancer and blood cells on the slides, the scientists next tested mixtures containing white blood cells and different concentrations of breast cancer cells. They could capture 95% of the cancer cells in these mixtures. Finally, they flowed cancer cells through a microfluidic device to test the strength of the adhesion of the cells to etched surfaces. Compared to circulating blood cells, cancer cells adhered nearly 100 times more tightly to roughened glass surfaces, Fu says.

By avoiding the use of antibodies, Fu says, this capture process could help researchers fish out a full range of circulating tumor cells from blood, regardless of which molecules the cells express on their membranes. The result would be a more complete understanding of tumor biology and metastasis, he says.

Toner says the researchers’ initial results are good, but points out that only tests using patient samples would prove the method’s usefulness. Actual blood samples include many cell types and contain far fewer cancer cells than any of the mixtures the scientists tested. The team is working with oncologists and cancer biologists to do tests on real patient samples, Fu says.