The study, which was led by Sendurai Mani, Ph.D., an associate professor of Translational Molecular Pathology and Jeffrey Chang, Ph.D., assistant professor of Integrative Biology at The University of Texas Health Science Center at Houston, discovered that tumors resembling six-day-old mice embryos are more likely to metastasize in comparison with standard tumors. The team found that the same genes that are turned on in developing mice also exist in metastasized tumors.
Each cell contains the same genetic set, however, activated genes are exclusive across tissues and diseases. This activation pattern its called the gene expression signature, indicates diseases’ subtypes, and are able to predict prognosis and disease survival.
“Looking at the embryo to learn more about cancer is a novel and important finding for researchers,” said Mani in a recent press release. “It is difficult to predict metastasis by merely analyzing the primary tumor and often, no mutations can be found. Clinicians still need to know whether a tumor is going to metastasize.”
Using gene expression signatures, scientists isolated a specific marker and were able to discover based on the biology of a developing embryo a specific marker.
The epithelial-mesenchymal transition (EMT) is a process that is activated in the early development of embryos. The tumors that are created in the linings of organs known as epitheliums account for about 85% of the solid tumors, and are responsible for activating this biochemical process, which was found to lead to metastasis. The researchers discovered that the EMT gene expression signature was not predictive of metastasis in human tumors.
For tumor calls to metastasize, they have to change their features. Cancer cells in the primary tumor develop very quickly and then they enter a “migratory state” where they metastatize. To identify the spread of a tumor, scientists need to switch back to a cell that is growing fast, a process called “plasticity.”
“Recent findings have shown that carcinomas have to shed off their EMT features and activate the reverse process, MET, in order to promote metastasis and create heterogeneous tumors at distant sites,” said Mani.
The team of researchers questioned whether tumors prone to spread would have a behavior similar to early-stage embryos.
“During early stages of embryo development, this phenomenon of plasticity is more prevalent compared to that in embryos at later stages or even in adult tissues, and our findings clearly demonstrate that metastatic tumors bear remarkable similarities in gene expression profiles to that of mouse embryos at day 6.5 of early gestation,” said Mani.
“Our findings clearly demonstrated that metastatic tumors are more like the embryo,” he said. “We found that tumors having gene expression signatures similar to mouse embryonic development day 6.5 were more prone to develop metastasis compared to tumors with more adult-differentiated signatures.”
The study will be published in the journal Nature Scientific Reports.