One of the main objectives of current cancer research is to stop metastatic, which is the spread of cancer cells beyond their initial site. The majority of malignant tumor cells use aberrant blood vessel leakage as a means of metastasizing. The alignment of endothelial cells, which line blood vessels, is a topic of recent research that aims to better understand how cancer spreads.
Researchers from the University of Michigan-Dearborn, Rensselaer Polytechnic Institute, and the University at Albany (SUNY) created a model that examines the local communication between tumor cells and endothelial cells and its effects on endothelial cell orientation in APL Bioengineering, published by AIP Publishing. Breast epithelial tumor cell lines and human umbilical vein endothelial cells (hUVECs) are co-cultured in this method to mimic the tumor-endothelial interaction.
According to author Jie Fan, “the blood arteries in tumor tissues are significantly more leaky than those in normal tissues.” We’re interested to know if tumor cells can impair endothelial cells’ tendency to face in a clockwise direction and lead them to become disorganized in the vessel.
The research builds on recent studies that indicated endothelial cells exhibit chirality, a form of mirror-image orientation resembling right and left hands, and have a propensity to tilt clockwise.
The strong clockwise chirality of endothelial cells, according to Fan, is crucial to maintaining the integrity of blood vessels, but regrettably, tumor cells may decrease or disrupt it, which may raise the possibility of metastasis. By bolstering the chirality and the integrity of the blood vessel’s endothelial barrier, maintaining normal chirality could prevent tumor transmigration.
The team co-cultured hUVECs with a number of tumor cell lines with various levels of malignancy to try to answer the question. Then, they contrasted the responses of hUVECs when tumor cells directly touched them with those when they did not. They used a contact printing technique to make donut- or figure-eight-shaped micropatterns to contain the cells in order to exercise this level of control.
The team discovered that direct physical contact with tumor cells had a greater impact on the clockwise chirality of the hUVECs than local hormone signaling did. The alteration of the hUVECs’ clockwise chirality appeared to be caused by some proteins on the tumor cell interacting with other proteins on endothelial cells.
The shifting of the cell types startled the group. The majority of metastatic cancer models assume that tumor cells move in the direction of blood vessels before penetrating through to the bloodstream.
Fan stated, “We had anticipated the tumor cell would infiltrate the endothelium cell.” However, we discovered that the endothelial cells on the micropattern were traveling in the direction of the tumor cell.
Fan stated that manipulating this connection has the potential to better control cancer spread, and he expects to continue working on the development of medicines in this direction.
