Blood vessels that supply oxygen and nutrients to tumors can also deliver something else - a signal that strengthens nearby cancer cells, making them more resistant to chemotherapy, more likely to spread to other organs and more lethal, scientists at The University of Texas MD Anderson Cancer Center report online in Cancer Cell.
Working in human colorectal cancer cell lines and tumor samples, as well as mouse models, the researchers found that endothelial cells, which line the inside of blood vessels, can trigger changes in cancer cells without even coming into direct contact with them.
This signaling by the endothelial cells causes colorectal cancer cells to take on the attributes of cancer stem cells, said Lee M. Ellis, M.D., professor in MD Anderson's Departments of Surgical Oncology and Cancer Biology and senior author of the paper.
"Cancer stem cells initiate and sustain tumor growth, promote metastasis and resistance to chemotherapy and have a variety of other attributes," Ellis said. "We've identified a new way that elements of a tumor's microenvironment, in this case endothelial cells, promote the conversion of malignant cells into cancer stem cells."
The team found the blood vessel cells use a previously unknown method of activating the Notch molecular pathway in colorectal cancer cells to initiate that conversion.
Possibilities for Notch-inhibiting drugs
Notch is a receptor protein found on a cell's surface that had been thought to be activated only by ligand proteins on the surface of other cells. Cell-to-cell contact was required. Notch is important to many cellular functions, including formation of new blood vessels, but it is often haywire in cancers.
"Our findings imply that Notch inhibitors under development and now in clinical trials might be able to affect tumor cells directly, through their vasculature, or both" Ellis said.
Colorectal cancer is the second-leading cause of cancer death in the United States, with 50,000 deaths caused annually by untreatable metastatic disease. A tumor's microenvironment, which includes blood vessels, supportive tissue and conditions such as hypoxia - lack of oxygen - is the soil that nurtures the metastatic tumor seed.