Experts at the University of Texas MD Anderson Cancer Center have discovered an unusual similarity between embryos and breast tumors in mice, and their findings could give doctors a new technique to gauge the cancer’s ability to spread (its metastatic propensity).
Writing in the latest edition of the journal Scientific Reports, Dr. Sendurai Mani, an associate professor of translational molecular pathology, and Dr. Jeffery Chang, an assistant professor of integrative biology, found that tumors closely resembling the six-day-old embryos of mice were more likely to metastasize than those resembling tissue from adult mice.
Specifically, they found that the same genes that are activated in developing mice can also be found in metastatic tumors, and even though every cell contains the same set of genes, the ones that are activated are unique across different tissues and medical conditions.
This pattern is known as a gene expression signature and could be used to help predict the survival odds or overall prognosis of diseases like cancer. Gene expression signatures are also believed to be useful in identifying treatments for certain patients, the authors added.
As Dr. Mani explained in a statement, “Looking at the embryo to learn more about cancer is a novel and important finding for researchers. 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.”
Gene signatures linked to metastasis in breast tumors
He and Dr. Chang looked to isolate one marker from the gene expression signature, and to identify one marker based on the biology of a developing embryo. First, they examined a process known as epithelial-mesenchymal transition (EMT), which is activated in early embryonic development and can be activated by tumors that form in the lining of the epithelium.
While the EMT gene expression signature can result in metastasis in the lab, they found that it did not predict metastasis in human tumors. However, the researchers pointed out that, in order for cancer cells to metastasize, they have to alter their characteristics. In primary tumors, cancer cells must grow quickly before they stop growing and enter a “migratory state” in which they disseminate to the metastatic site, where they change back into a fast-growing cell.
This ability to change characteristics is known as plasticity, and recent research has demonstrated that carcinomas switch off their EMT features and activate the opposite process (known as MET) to promote metastasis. This led Dr. Mani and his co-authors to wonder if those tumors that were more likely to spread were more likely to behave like 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,” he explained, “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.”
“Our findings clearly demonstrated that metastatic tumors are more like the embryo,” Dr. Mani added. “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.”
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