Researchers from Johns Hopkins Institute for NanoBioTechnology are visualizing many of the steps involved in how cancer cells break free from tumors and travel through the blood stream, potentially on their way to distant organs. Using an artificial blood vessel developed in the laboratory of Peter Searson, INBT director and professor of materials science and engineering, scientists are looking more closely into the complex journey of the cancer cell.
INBT’s science writer, Mary Spiro, interviewed device developer Andrew Wong, a doctoral student Searson’s lab, for the NanoByte Podcast. Wong is an INBT training grant student. Listen to NANOBYTE #101 at this link.
Wong describes the transparent device, which is made up of a cylindrical channel lined with human endothelial cells and housed within a gel made of collagen, the body’s structural protein that supports living tissues. A small clump of metastatic breast cancer cells is seeded in the gel near the vessel while a nutrient rich fluid was pumped through the channel to simulate blood flow. By adding fluorescent tags the breast cancer cells, the researchers were able to track the cells’ paths over multiple days under a microscope.
VIDEO: Watch how a cancer cell approaches the artificial blood vessel, balls up and then forces its way through the endothelial cells and into the streaming fluids within the channel of the device. (Video by Searson Lab)
The lab-made device allows researchers to visualize how “a single cancer cell degrades the matrix and creates a tunnel that allows it to travel to the vessel wall,” says Wong. “The cell then balls up, and after a few days, exerts a force that disrupts the endothelial cells. It is then swept away by the flow. “
Wong said his next goal will be to use the artificial blood vessel to investigate different cancer treatment strategies, such as chemotherapeutic drugs, to find ways to improve the targeting of drug-resistant tumors.
Results of their experiments with this device were published in the journal Cancer Research in September.
Check out this gallery of images from the Searson Lab. The captions are as follows:
Figure 1. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a functional vessel immunofluorescently stained for PECAM-1 (green) and nuclei (blue).
Figure 2. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a vessel with dual-labeled MDA-MB-231 breast cancer cells on the periphery.
Figure 3. Phase-contrast and fluorescence overlays depicting a functional vessel comprised of human umbilical vein endothelial cells (HUVECs) with dual-labeled MDA-MB-231 breast cancer cells on the periphery (green in the nucleus, red in the cytoplasm).