For the majority of cancer patients, it?s not the primary tumor that is kills, but the spread of cancer cells or metastasis from the primary tumor to secondary locations throughout the body that is deadly. That?s why a researchers involved in contemporary cancer research are now focusing on how to stop or fight metastasis.

While metastasis ranks among the most lethal of all cancer-associated processes, on the molecular level, it remains one of the least well understood. In a number of previous laboratory studies, researchers suggest that metastasizing cancer cells undergo a major molecular change when they leave the primary tumor ? a process called epithelial-to-mesenchymal transition (EMT). 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. But so far, confirmation of the EMT process has only taken place in test tubes or in animals and not in humans.

As a biological process, EMT is an essential component of embryonic development and allows for reduced cell adhesiveness and increased cell movement.

…metastasizing ovarian cancer cells are very different from those comprising the primary tumor and will likely require new types of chemotherapy…

Evidence of epithelial-to-mesenchymal transition
In a new study, published in the Journal of Ovarian Research, Georgia Tech scientists have direct evidence that EMT takes place in humans, at least in ovarian cancer patients. [1] The findings suggest that doctors should treat patients with a combination of drugs: those that kill cancer cells in primary tumors and drugs that target the unique characteristics of cancer cells spreading through the body.

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Matching tissue
Using gene expression profiling (Affymetrix, U133), the researchers looked at 14 matching sets of primary (ovary) and metastatic (omentum) ovarian cancer (serous adenocarcinoma) patient samples (ovarian and abdominal cancerous tissues) in seven patients. Pathologically, the cells looked 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. The scientists didn?t see the process take place, but they know it happened.

An analyses of the research data focusing on genes previously associated with EMT clearly distinguished the primary from metastatic samples in all but one patient.

Increased Cell Movement
?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 John McDonald, PhD, director of Georgia Tech?s Integrated Cancer Research Center and lead investigator on the project. ?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.?

Very different
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.?

Promising findings
Ovarian cancer is the most malignant of all gynecological cancers and responsible for more than 14,000 deaths annually in the United States alone. It often reveals no early symptoms and isn?t typically diagnosed until after it spreads. ?Our team is hopeful that, because of the new findings, the substantial body of knowledge that has already been acquired on how to block EMT and reduce metastasis in experimental models may now begin to be applied to humans,? said Georgia Tech graduate student Loukia Lili, co-author of the study.

For more information
[1]Lili LN, Matyunina LV, Walker LD, Wells SL, Benigno BB, McDonald JF. Molecular profiling supports the role of epithelial-to-mesenchymal transition (EMT) in ovarian cancer metastasis.J Ovarian Res. 2013 Jul 10;6(1):49. doi: 10.1186/1757-2215-6-49.[Article][PubMed]

Photo:John McDonald, co-director of the Ovarian Cancer Institute. Photo Courtesy:Georgia Institute of Technology

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