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| Simon Grelet, Ph.D., assistant professor of biochemistry and molecular biology, and Sapthala Loku Galappaththi, a doctoral student, work in the lab at the Mitchell Cancer Institute. |
Cancer innervation, also known as cancer neurogenesis, is the process of the peripheral nervous system infiltrating primary cancer, which can lead to enhanced tumor growth and poor outcomes for patients as observed within several types of cancer.
The newly developed methodology, Grelet said, led his team to make a first discovery about cancer biology to foster medical advancement.
“Using our new approach, we have also developed a new cell model of breast cancer aggressivity and highlighted how breast cancer harboring an aggressive phenotype can trigger robust differentiation of neuronal precursors,” Grelet said. “This finding supports our previous recent research, demonstrating how mesenchymal-type cancer cells can promote cancer innervation, supporting increased cancer metastasis.”
Until now, Grelet said, the study of how cancer cells promote cancer innervation has been hindered by a lack of streamlined methods, creating difficulties in comparing data among research groups. “Each lab tends to develop its own methodology,” he said, “leading to variations that make comprehensive analysis challenging. Moreover, previous methods did not lend themselves to high-throughput screening methods, such as drug or genetic screenings, limiting the progress in this area.”
Because of that, researchers could only study tens to a maximum of hundreds of cells, Grelet said. Now, with the method developed by the USA team, researchers could easily analyze millions of cells within minutes. In this study, Grelet developed a CRISPR-based genetic reporter methodology that aims to address the issue.
Overall, Grelet said, the novel approach allows researchers to examine cancer-induced neural differentiation, which is a preliminary step of cancer innervation, in a more efficient and standardized manner. “This advancement opens up the possibility for high-throughput screening methods and will enable faster and more consistent research progress,” he said. In the future, Grelet expects this technology will help to identify new therapeutic targets involved in cancer innervation.
Other authors of the research paper were Sapthala Loku Galappaththi, a Ph.D. student who joined Grelet’s lab in 2022; Brenna Katz, a medical student at the Whiddon College of Medicine who participated in the study in 2022 as part of the Medical Summer Research Program; Gregory Hoover, a senior research technologist; and Patrick Howze, a former USA student who recently became a researcher at the University of Alabama at Birmingham.
“It was a wonderful teamwork experience,” Grelet said, “where students as well as skilled research assistants worked alongside us playing a crucial role in our work by managing our labs and training the students in new techniques.”
Grelet joined the Whiddon College of Medicine and the Mitchell Cancer Institute in 2020 after completing postdoctoral studies at the Hollings Cancer Center, Medical University of South Carolina in Charleston. He earned a Ph.D. from the French National Institute of Health and Medical Research at Reims University in France.
The research was supported by startup funds from the Department of Biochemistry and Molecular Biology at the Whiddon College of Medicine and the Mitchell Cancer Institute; the Mitchell Endowment and the Patricia Cobb Rodgers Endowment from the Whiddon College of Medicine. Other resources and services were provided by the Bioimaging Core Facility and the Flow Cytometry Shared Resource Laboratories, both core research facilities supported by the Whiddon College of Medicine.
