Under the Microscope: Researchers zoom in on cancer cells to find out how they spread

Head and neck cancers are particularly devastating because they often affect the way a patient looks, as well as crucial functions such as eating and speaking.

“For a long time, head and neck cancers were thought of as resulting from poor choices such as smoking or drinking, which unfortunately led to a dearth of funding in this area,” said V Foundation Scholar Sidharth Puram, M.D., Ph.D., from Washington University School of Medicine. “Now, there’s a growing recognition that studying head and neck cancers is important, and this is creating opportunities to make major strides in understanding these cancers so that better treatments can be developed.”

As a head and neck surgeon, Puram is acutely aware of the ostracization and stigmatization patients with these cancers can experience. This has motivated his quest to better understand how and why head and neck cancers sometimes spread, or metastasize. His work could eventually lead to new therapies or allow doctors to tailor treatments based on whether a tumor is likely to spread.

Looking at what makes cancer spread

The new project expands on findings from a previous study in which Puram and his colleagues analyzed gene expression in head and neck cancers in individual cells, one of the first single-cell analyses of its type to be performed on solid tumors.

“Our previous single-cell work revealed that a subset of cells appears to be particularly important for invasion and metastasis,” said Puram. “These cells undergo what is called a partial epithelial to mesenchymal transition (partial EMT), which means they change in a way that allows them to ultimately spread.”

With the V Foundation funding, the researchers studied these partial EMT cells in detail to find out how they work and what protein markers could be used to identify them. In collaboration with Shannon Stott, Ph.D., and her group at Massachusetts General Hospital, they used a new technology known as multi-spectral imaging that allows simultaneous, high-resolution imaging of up to 15 cell markers across a tissue section that may contain thousands of cells.

“We used this approach to analyze millions of cancer cells from around 10 different tumor samples,” said Puram. “We sought to answer important questions such as how do markers that relate to partial EMT drive metastasis?”

The spectral analysis helped the researchers pinpoint a group of partial EMT markers that appear to play a role in metastasis. It also showed that partial EMT cells might hide from the body’s immune system, perhaps allowing them to avoid destruction and most likely contributing to their ability to spread. A collaboration with Itay Tirosh, Ph.D., and his group at the Weizmann Institute of Science also revealed that cells undergo partial EMT in other types of tumors beyond head and neck cancers.

Working toward better treatment

“In terms of clinical translation, we think that the presence of partial EMT cells could be useful as a readout of cancer aggressiveness, which could allow doctors to dial in the treatment that appropriately matches that aggressiveness,” said Puram. “As we keep learning more about the partial EMT process, it might also be possible to develop a drug that targets partial EMT to make tumors less aggressive or prevent metastasis.”

Puram says that the V Foundation funding made it possible to generate the preliminary data that is critical for securing additional grants. It also helped set up his lab with the tools and personnel necessary for working toward translating their research into the clinic. The funding has already led to a new study in which the researchers will scale up the multi-spectral imaging analysis by examining 200 new tumor samples. This will help them find out whether patients with partial EMT cells are more likely to have poor outcomes or show resistance to treatment, for example.

“Funding for head and neck cancer research is very important because of how much catching up we have to do in our field compared to other tumors,” said Puram.

We’re grateful that the V Foundation supports research in this area. Their funding provided a strong impetus for us to engage in a major line of investigation using imaging-based approaches to study cell-cell interactions in head and neck cancer.

Sidharth Puram, M.D., Ph.D.