Preventing metastasis — the development of cancer cells outside their original site — remains one of the main goals of current cancer research. Most malignant cancer cells metastasize by exploiting abnormal leakage from blood vessels. The new work looks to further explore how the alignment of endothelial cells, which line blood vessels, plays a role in the spread of cancer.
in APL BioengineeringBy AIP Publishing, researchers from the University of Michigan-Dearborn, Rensselaer Polytechnic Institute, and the University at Albany-SUNY have developed a model that examines local communication between endothelial cells and tumor cells and its effects on endothelial cell orientation. The approach involves using co-cultured human umbilical vein endothelial cells (hUVECs) and breast epithelial tumor cell lines to mimic the interaction between tumor and endothelium.
“The blood vessels in tumor tissue are more leaky than those in normal tissue,” said author Ji Fan. “We’re curious about whether cancer cells can cause the clockwise weakening of endothelial cells and cause them to become irregular in blood vessels.”
The work expands on recent findings showing that endothelial cells have divergence, a type of mirror image orientation similar to right and left hands, and tend to deviate in a clockwise direction.
“We think that the strong clockwise symmetry of endothelial cells is important for maintaining the integrity of blood vessels, but unfortunately, they can be damaged/weakened by cancer cells, which can increase the risk of metastasis,” Fan said. “Maintaining normal contrast can prevent tumor metastasis by enhancing the contrast and integrity of the vascular endothelial barrier.”
To address the question, the group cultured hUVECs with a series of cancer cell lines of varying degrees of malignancy. They then compared how the hUVECs responded when the cancer cells were touching them directly versus not. To exert such a degree of control, they used the seam printing technique to create small donut- or figure-of-eight patterns to retain cells.
The group found that the clockwise transduction of hUVECs was influenced less by local hormone signals and more by direct physical contact with tumor cells. Certain proteins on tumor cells bind to others on endothelial cells appear to play a role in altering the clockwise reproductive symmetry of hUVECs.
The group was surprised by the movement of cell types. In most models of metastasis, cancer cells are thought to travel towards the blood vessels before they penetrate the bloodstream.
“We expected the cancer cell to invade the endothelial cell,” Fan said. “However, we found that the endothelial cells were moving towards the cancer cell on the little tap.”
Fan said that regulating this interaction holds promise for improving control of cancer metastasis and he hopes to work further on developing treatments to that end.