For the majority of cancer patients, it is not the primary tumor that is deadly but the metastasis of cancer cells from the primary tumor to secondary locations throughout the body. A new study provides the first direct evidence that the deadly epithelial-to-mesenchymal transition (EMT) occurs in humans during metasis, at least in patients with ovarian cancer.
Previous laboratory studies had suggested that metastasizing cells undergo EMT, which is a major molecular change, when they leave the primary tumor. As the cells travel from one site to another, they pick up new characteristics. More importantly, they develop a resistance to chemotherapy that is effective on the primary tumor.
The new findings, published in Journal of Ovarian Research (2013; doi:10.1186/1757-2215-6-49), suggest that doctors should treat patients with a combination of drugs: those that kill cancer cells in primary tumors and those that target the unique characteristics of cancer cells spreading through the body.
The research team, led by John MacDonald, PhD, director of Georgia Tech University’s Integrated Cancer Research Center in Atlanta, looked at matching ovarian and abdominal cancerous tissues in seven patients. Pathologically, the cells appeared exactly the same, implying that they simply fell off the primary tumor and spread to the secondary site with no changes. But on the molecular level, the cells were very different. Those in the metastatic site displayed genetic signatures consistent with EMT. Though the scientists did not observe the process occurring, they inferred it happened.
“It’s like noticing that a piece of cake has gone missing from your kitchen and you turn to see your daughter with chocolate on her face,” said McDonald. “You didn’t see her eat the cake, but the evidence is overwhelming. The gene expression patterns of the metastatic cancers displayed gene expression profiles that unambiguously identified them as having gone through EMT.”
The EMT process is an essential component of embryonic development and allows for reduced cell adhesiveness and increased cell movement.
According to Benedict Benigno, MD, collaborating physician on the paper, CEO of the Ovarian Cancer Institute, and director of gynecological oncology at Atlanta’s Northside Hospital, “These results clearly indicate that metastasizing ovarian cancer cells are very different from those comprising the primary tumor and will likely require new types of chemotherapy if we are going to improve the outcome of these patients.”