Remodeling of the Extracellular Matrix by Adrenocortical Carcinoma to Promote Metastasis
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Date
2024-05
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The Ohio State University
Abstract
Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy affecting the adrenal cortex. Treatments such as surgery and chemotherapeutic agents exist to treat the cancer; however, survivability remains low due to their ineffectiveness. Survivability is also low due to the tendency for the disease to metastasis prior to diagnosis. Additionally, it is hard to develop new therapeutics because current animal and many in vitro models are not accurate since they fail to mimic interactions that are seen in vivo. In this project, lung fibroblasts and bronchial epithelial cells will be cultured in a 3D hydrogel to simulate the lung microenvironment and then exposed to regular media or media that was conditioned by ACC cells to see how the ECM is remodeled in distant tissues prior to metastasis. After culturing, histology and staining will be done to evaluate the difference in collagen, and F-actin and smooth muscle from exposure to secreted factors. Additionally, the stiffness of the gel will be calculated through mechanical testing. Finally, this setup will be transferred to a microfluidic device to examine how ACC cell invasion changes when the secondary site is exposed to ACC secreted factors.
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Keywords
metastasis, Adrenocortical carcinoma, extracellular matrix, cancer, remodelling, microfluidic device