Novel Stirring Technique Improves Cancer Motility Analysis

Researchers in Japan have described a new, non-invasive way to measure the invasive capacity of tumors that could provide valuable insights for therapeutic strategies.

Currently, the motility and invasiveness of cancer cells is assessed biochemically with a method called Rac/Cdc42 pull-down assay. Rac and Cdc42 are well-studied, low molecular weight G proteins that regulate the ability of cancer cells to move, a measure of its invasive capacity. More active Rac and Cdc42 makes it more likely that diseased cells will invade and metastasize in blood and lymph vessels.

However, when using this approach, the positional information within the cancer tissue is completely lost, and it is also impossible to evaluate the heterogenicity of the cells.

A new method developed by a research team at Hokkaido University and described in Scientific Reports has successfully evaluated the motility and invasive capacity of cancer tissue sections removed from colorectal cancer patients without losing this valuable information. Using a recently developed non-contact technology in which alternating electrical fields are used to ‘stir’ liquid droplets at extremely high speeds, the team agitated a solution containing molecular probes that bind to activated Rac/Cdc42 on FFPE specimens.

The method revealed many insights about the Rac/Cdc42 activity of cells. They found that Rac/Cdc42 activity was significantly higher in the tumor area than in the normal mucosa of the colon, and that the more advanced the cancer cell stage, the greater the increase in Rac/Cdc42 activity. This increase was particularly high at the leading edges of the tumor, where cancer cells infiltrate the surrounding healthy tissue. Additionally, in cases where Rac1/Cdc42 activity was high, there was a strong tendency for lymphatic invasion.

“This technology is effective for breast cancer and brain tumors as well as colorectal cancer, and it promises to provide useful information for predicting lymph node metastasis and for the assessment of Rac inhibitor-based therapies in the future,” says Masumi Tsuda, associate professor in the Department of Cancer Pathology, Faculty of Medicine, Hokkaido University/Institute for Chemical Reaction Design and Discovery.