The Arkansas Integrative Metabolic Research Center (AIMRC) has received a $263,813 Women's Health Supplement award from the National Institutes of Health to explore how obesity-induced changes in tissue structure affect nerve growth in breast tumors.

Younghye Song, Ph.D., assistant professor of biomedical engineering in the College of Engineering, will be the project lead for this supplement award. Dr. Song is an expert in the development of tissue-engineered models of the breast tumor microenvironment. These tissue-engineered models are tissue-like structures that are fabricated using altered biological materials and allow the study of different diseases, like cancer, using more realistic representations of tissue.

Breast tumor innervation is increasingly gaining attention as an important feature of malignant transformation of the ecosystem surrounding a tumor. Neuroscience and nerve repair fields have shown, including recent work from Song, that nerve fibers grow more easily when the surrounding support structure in the tissue is aligned. Since adipose, or fat tissue, is heavily innervated (supplied with nerves), and obese adipose is marked with aligned extracellular matrix topography, which enhances neurite outgrowth, obesity may worsen breast cancer in part by promoting breast tumor innervation (BTI). An increase in the number of nerves growing into the tumor may act like a cancer"'highway" upon which breast cancer can spread to other parts of the body (metastasis). "Given that obesity is a great risk factor for breast cancer, and that tumor innervation is linked with worse prognosis of the disease, investigating a potential link between the two will further broaden our understanding of breast cancer progression in obese patients," Song said.

The overall goal of this project is to investigate the effect of obesity on breast tumor tissue structure changes and how this affects nerve growth (innervation). No other research groups to date have demonstrated the use of advanced tissue-engineered cultures combined with longitudinal, label-free imaging to study tumor metabolism links to innervation in the context of obesity. The combination of two modalities (tissue-engineered tumor microenvironment and optical redox imaging) as well as the investigation of a link between obesity, metabolism and tumor innervation presents innovation in both technology and approach to answering an underappreciated yet critical aspect of tumor malignancy. This research aligns with the National Cancer Institute's focus on understanding the fundamental mechanisms of cancer, as well as the Office of Research on Women's Health's commitment to addressing women's health issues, particularly chronic diseases, and comorbidities like obesity.

This funding will enable Dr. Song and the AIMRC to continue research on breast tumor innervation, setting the stage for future studies that more accurately replicate the tumor microenvironment by incorporating adipocytes into 3D cultures and using cells from lean and obese subjects. "I'm grateful for this supplement award for allowing my lab to expand our line of research on breast tumor innervation using our tissue-engineered models and advanced imaging modalities available at the AIMRC," Song said.

About AIMRC: The Arkansas Integrative Metabolic Research Center (AIMRC) was established in April 2021 with Phase I COBRE funding from NIGMS (P20GM139768). The AIMRC is a research center located at the University of Arkansas focused on understanding the role of cell and tissue metabolism in disease, development, and repair through research involving advanced imaging, bioenergetics, and data science.