Cells that line the blood vessels, known as endothelial cells, were once thought to act primarily as gates, regulating delivery of blood to and from tissues. But today we know they do much more. In the early 1990s, researchers including Elazer Edelman ‘78, SM ‘79, PhD ‘84, now a professor in the MIT-Harvard Division of Health Sciences and Technology (HST), showed that endothelial cells regulate blood clotting, tissue repair, inflammation, and scarring.
More recently, Edelman and HST graduate student Joseph Franses discovered a new role for endothelial cells: they secrete molecules that suppress tumor growth and keep cancer cells from invading other tissues, a finding that could lead to a new way to treat cancer.
Edelman theorizes that there is a constant struggle between cancer cells and endothelial cells. Most of the time the endothelial cells triumph, but when they fail, cancer can develop and spread. Implanting new endothelial cells adjacent to a tumor could shrink the tumor or prevent it from growing back or spreading further after surgery or chemotherapy, he says. Edelman has already tested such an implant in mice, and MIT has licensed the technology to Pervasis Therapeutics, which plans to test it in humans.
Edelman describes the work, which appeared in the journal Science Translational Medicine, as a “paradigm shift” that could fundamentally change how cancer is understood and treated. “This is a cancer therapy that could be used alone or with chemotherapy, radiation, or surgery, but without adding any devastating side effects,” he says.
Edelman, Franses, and their colleagues showed that secretions from endothelial cells inhibit the growth and invasiveness of tumor cells both in vitro and in mice. These secretions contain hundreds of biochemicals, but the researchers identified two that are particularly important: a large sugar-protein complex called perlecan and a cytokine called interleukin-6 (IL-6). When endothelial cells secrete large amounts of perlecan but little IL-6, they can keep cancer cells at bay.
For this study, the researchers used a scaffold that Edelman developed several years ago, made of denatured, compressed collagen (a protein that makes up much of human connective tissue). Endothelial cells are grown on the scaffold, which is then implanted around blood vessels. In mouse studies, those cells significantly slowed tumor growth and prevented distant metastases. “Replacing the endothelial cells with implanted cells restores control, and in a sense it is like replacing the cellular policeman that should reside on the corner of every tumor neighborhood,” says Franses.