Killer wound-healing; stress and ovarian cancer; blood vessels' bad signals
A key to the perils of endless injury repair, the molecular path from stress through a cancer-promoting gene to ovarian cancer progression, and signals by endothelial cells that strengthen colorectal cancer are among recent discoveries by MD Anderson researchers.
By uncovering these new connections, scientists expose new potential targets for fibrosis, the lethal scarring of organs, and cancer.
Endothelial cells make cancer cells tougher, more dangerous
Blood vessels feeding colorectal cancer tumors are delivering more than oxygen and nutrients. They also flip a molecular switch that sends a signal to nearby cancer cells telling them to convert to colorectal cancer stem cells.
"Cancer stem cells initiate and sustain tumor growth, promote metastasis and resistance to chemotherapy and have a variety of other attributes," says Lee Ellis, M.D., of MD Anderson's Department of Surgical Oncology. The blood vessels cells activate Notch signaling. Drugs in clinical trials attack Notch.
The hormone noradrenaline turns on the oncogene Src, which promotes ovarian cancer growth and spread through beta-adrenergic (ADRB) receptors expressed on tumor cells.
"When Src is triggered by stress, it works like a dam letting out water that causes a flood downstream. Src, like the dam, is a master regulator switch that causes a chain reaction in the cells," says Anil Sood, M.D., of the departments of gynecological medical oncology and cancer biology. One implication: beta blockers might work against ovarian cancer.
News release and Nature Communications paper
Protein plays pivotal role in scarring that destroys organs
When the body's wound-healing process gets endlessly turned on, the tissues that provide a scaffold for injury repair can destroy the kidneys, liver and lungs. This process, known as fibrosis, also is tightly tied to cancer.
"Fibrosis is wound-healing that never stops. The body thinks an injury exists when it doesn't, so it just keeps going, producing scars that clog an organ's system and destroy its functional tissue until it fails," says Raghu Kalluri, Ph.D., M.D., chair of the Department of Cancer Biology. Kalluri and colleagues identified the role of HE4 in promoting fibrosis. A test already approved for ovarian cancer detects HE4 levels in the blood.