image: Researchers noticed that cancer cells crowded back-to-back -- high density -- were less effective at invading cancer-free tissue than cells grown in a low density -- less crowded -- environment. view more
Credit: Courtesy Ghada M. Sharif/Georgetown
WASHINGTON -- Cancer cells crowded tightly together suddenly surrender their desire to spread, and this change of heart is related to a cellular pathway that controls organ size. These two stunning observations are reported today by researchers at Georgetown Lombardi Comprehensive Cancer Center in the journal Oncogene.
"What we really need in cancer treatment is a way to stop cancer from growing in the organ it has spread to, and we have discovered a mechanism that seems to do that," says the study's senior investigator, Anton Wellstein, MD, PhD, a professor of oncology and pharmacology at Georgetown Lombardi.
Wellstein says the initial finding was made when Ghada M. Sharif, PhD, a member of the Wellstein lab, noticed that cancer cells crowded back-to-back -- high density -- were less effective at invading cancer-free tissue than cells grown in a low density -- less crowded -- environment.
It turns out that high-density cells activated the "Hippo" molecular pathway, an ancient biological mechanism that limits the size of an organ. Low-density cancer cells do not engage Hippo, which means the cells are free to grow unchecked within the organ. The trigger for activating Hippo is a single molecule called YAP.
"What was very surprising to us was that this pathway is active in cancer cells," says Wellstein.
"You can make the same cancer cells become invasive or not, depending on whether that pathway is activated--which is fascinating," he says. "Invasive and non-invasive cells are genetically the same. What's different is whether the Hippo pathway is active."
He says experiments show the mechanism is common to a variety of cancers, including breast, prostate, pancreatic and lung.
"We think cancer cells go wild, they just take off. They will invade and there is nothing you can do about it," he says. "But it actually turns out that crowded cells still have that memory of how good citizens -- good cells -- behave, and that was a big surprise to us. That is why this finding is quite significant."
Because many cancers metastasize early in their development, a drug based on the Hippo pathway could be used to limit their spread within the organs the cancer spreads to, he says.
"We have figured out a mechanism that is crucial for cancer cell invasion and metastasis, and we have found the driver of that mechanism, but there is still much work to do," Wellstein says.
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Other authors contributing to the study are Marcel O. Schmidt, PhD, Chunling Yi, PhD, Zhangzhi Hu, MD, Bassem R. Haddad, MD, Eric Glasgow, PhD, and Anna T. Riegel, PhD, all from Georgetown Lombardi.
The study was supported by National Institutes of Health/National Cancer Institute grants (CA71508, CA113477, and CA51008).
About Georgetown Lombardi Comprehensive Cancer Center
Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 41 comprehensive cancer centers in the nation, as designated by the National Cancer Institute (grant #P30 CA051008), and the only one in the Washington, DC area. For more information, go to http://lombardi.georgetown.edu.
About Georgetown University Medical Center
Georgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.
Journal
Oncogene