A trap for metastatic clusters of cancer cells
Researchers at the US National Institute of Biomedical Imaging and Engineering, working under the guidance of Professor Mehmet To, have developed a microfluidic chip capable of capturing clusters of tumor cells circulating in the blood. The study of these clusters will provide specialists with new data on the mechanisms of metastasis of malignant tumors.
Circulating cancer cells break away from the tumor and move with the blood flow through the patient's body. Single tumor cells are extremely rare in the bloodstream, usually their concentration is less than one cell per billion blood cells. Such cells can penetrate into the tissues of organs remote from the primary tumor and remain there. Experts believe that this mechanism is one of the variants of the cancer metastasis process.
Even rarer than single tumor cells are small groups or clusters of tumor cells. The existence of these clusters has been known for more than 50 years, but their prevalence in the blood and their role in the formation of metastases have not yet been properly studied mainly because of their elusiveness. However, recent advances in biomedical technologies that allow scientists to capture single tumor cells have revived interest in clusters, sometimes captured together with single cells.
A unique microfluidic chip or Cluster-Chip developed by the authors, which provides selective capture of tumor cell clusters in whole blood, can help in satisfying this interest.
An enlarged image of a circulating cluster of tumor cells captured by a Cluster-Chip.
A cluster of tumor cells labeled with a fluorescent dye,
balancing on top of a triangular ledge in a Cluster-Chip.
The chip device provides slow blood pumping through many rows of microscopic triangular protrusions arranged in such a way that every two protrusions direct cells to the top of the third. As a result, individual cells, including blood cells and single tumor cells, slide down the sides of the triangular protrusion and continue their movement along the chip. At the same time, clusters of cells linger on the sharp vertices of triangular protrusions.
To test the effectiveness of the new chip, the researchers injected it with blood containing clusters labeled with fluorescent dye, consisting of 2-30 tumor cells, and counted the number of delayed and missed clusters. At a blood flow rate of 2.5 ml/hour, the chip captured 99% of clusters consisting of 4 or more cells, 70% of three-cell clusters and 41% of two-cell clusters. Comparison of the state of intact and chip-captured clusters under a microscope showed that staying in the chip does not violate their integrity.
Comparison of Cluster-Chip with existing methods of isolating tumor cell clusters, such as pushing blood through a membrane filter and using tumor-protein-specific antibodies, demonstrated its higher efficiency.
The researchers also tested Cluster-Chip on blood samples from 60 patients with metastatic malignant tumors. As a result, clusters of tumor cells were found in the blood of 11 out of 27 (40.7%) patients with breast cancer, 6 out of 20 (30%) patients with melanoma and 4 out of 13 (31%) patients with prostate cancer. The large number of clusters in the samples, as well as the unexpectedly high frequency of their detection, indicate that their contribution to the metasticization process is most likely significantly greater than has been assumed so far.
The study of the biological characteristics of clusters has shown that they can include both actively proliferating and cells that have entered the phase of physiological aging. Moreover, in the clusters of some patients (less than 5%), the researchers found the presence of immune cells.
The authors believe that the Cluster-Chip developed by them will play an important role in the development of a new direction of research devoted to the study of the biology of tumor cell clusters. They hope that over time, the results of work in this direction will form the basis of methods for preventing metastasis of malignant tumors and the development of individual cancer treatment protocols.
Article A Fatih Sarioglu et al. A microfluidic device for label-free, physical capture of circulating tumor cell clusters is published in the journal Nature Methods.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the National Institutes of Health:
Microchip captures clusters of circulating tumor cells - NIH study.
19.05.2015