Breast tumors behave like mouse embryos

By John Murphy, MDLinx
Published December 23, 2015

Key Takeaways

Development of breast tumors mirrors the development of mouse embryos, say researchers at The University of Texas MD Anderson Cancer Center in Houston. Importantly, this unique discovery could not only help predict which breast tumors are likely to metastasize, but guide treatment options to increase patient survival.

The study, led by Sendurai Mani, PhD, Associate Professor of Translational Molecular Pathology and Jeffrey Chang, PhD, Assistant Professor of Integrative Biology at The University of Texas Health Science Center at Houston, found that tumors that resemble 6-day-old mouse embryos are more prone to metastasize than those that look like tissues from adult mice.

Specifically, they noticed that the same genes that are activated in developing mice are also present in metastatic tumors. Study results were published in the June 30 issue of Nature Scientific Reports.

This pattern of activation—called a gene expression signature—may indicate different subtypes of a disease, including those that predict disease survival or prognosis. Gene expression signatures are thought to be useful for identifying effective treatments for select groups of patients.

“Looking at the embryo to learn more about cancer is a novel and important finding for researchers,” Dr. Mani said. “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.”

To that end, the researchers wondered if tumors likely to spread would behave like embryos—in particular, early-stage embryos. One process that is activated in early embryonic development is called the epithelial-mesenchymal transition (EMT). But when tested in prior research, the EMT gene expression signature did not predict metastasis in human tumors. Other factors must be involved, they reasoned.

A key insight to this problem is that for cancer cells to metastasize, they must change their characteristics. In the primary tumor, cancer cells must grow quickly before they stop growing and enter a “migratory state” where they disseminate to the metastatic site. To establish tumor spread, they need to switch back to a fast-growing cell.

“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,” Dr. Mani said.

That is, metastatic cells must possess “plasticity.”

“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,” Dr. Mani said. “We found that tumors having gene expression signatures similar to mouse embryonic development [at] day 6.5 were more prone to develop metastasis compared to tumors with more adult-differentiated signatures.”

This first-of-its-kind signature stands out in its ability to predict metastatic propensity in cancer patients by analyzing the bulk of the primary tumor rather than residual issues or scarce circulating tumor cells. More importantly, the signature is applicable to a wide class of breast tumor subtypes.

Finally, the authors described a novel “score,” based on the unique gene expression signature, which can be applied to predict the metastatic capacity of breast tumor cells in vivo. “Directed prospective studies in the future will determine if this signature can indeed complement classic prognostic factors to improve patient outcome,” they concluded.

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