Researchers at the University of Maryland School of Medicine have developed a microfluidic device that could help preserve and detect the presence of thin membrane protrusions called “microtentacles” on breast cancer cells which can help image non-adherent cells to detect whether a tumour is likely to spread.
Microtentacles are thin membrane protrusions that extend from breast cancer cells and appear to play a key role in helping cancer cells spread from the original tumour and reattach themselves in distant organs.
A protein called “tau” promotes the formation of these microtentacles on breast tumour cells which break away from primary cancers and circulate in the bloodstream. However, formaldehyde which is typically used to chemically preserve cells taken from tissue biopsies destroys the fragile structure of the microtentacles.
The new gadget called TetherChip is a tiny device filled with fluid that is engineered to prevent cell adhesion with an optically-clear, thermal-crosslinked polyelectrolyte multilayer nanosurface and a terminal lipid layer. Cell adhesion can lead to the destruction of the microtentacles. Meanwhile, the lipid layer also helps tether the cell membrane to the device to immobilise the cell for better visualisation under a microscope.
“In our new study, we describe our new solution for preserving tumour cell samples on a pathology slide without destroying the microtentacles they may contain,” said a lead author Dr Martin. “Identifying and targeting these microtentacles on routine biopsies could be the next exciting frontier of cancer prognosis and treatment.”
The device remains stable for more than 6 months and can be shipped across the country for patients seeking consultations with other oncologists. The samples can be rapidly fixed and stained on TetherChips, so patients can receive their biopsy results on the day of their procedure.
While this technology was developed to analyse breast tumour cells, the researchers also found that TetherChips allows for the analysis of multiple tumour cell types, studies found that many tumours beyond breast cancer can also form microtentacles.
Detection of microtentacles might help choose better therapy for treating cancer, Dr Martin said.
“Some forms of chemotherapy given before surgery to shrink tumours might actually increase the chances of these tumours spreading if the cells contain microtentacles. Those patients may benefit more from immediate surgery to remove the tumour or from combination therapy with a drug that targets microtentacles for destruction,” he added.
Most chemotherapy drugs target cell division, aiming to slow or stop tumour growth. Dr Martin said his team previously found that a popular chemotherapy drug, Taxol, actually causes cancer cell microtentacles to grow longer and allows tumour cells to reattach faster, which may have important treatment implications for breast cancer patients. They are currently investigating how other cancer drugs influence microtentacles in an effort to determine whether this test can be used to change clinical practice.
“Determining the true role that microtentacles play in metastases remains an important avenue for research and could lead to important new advances in cancer treatment,” E. Albert Reece, Executive Vice President for Medical Affairs, UM Baltimore. “This is adding an important piece to the cancer puzzle that could help explain why some tumours that shrink from chemotherapy remain so deadly.”
The results are published in the Royal Society of Chemistry journal Lab on a Chip.