Decellularized Liver Biomatrices as a Model for 3D Cancer Metastasis
Abstract
Ovarian cancer is metastatic at the time of diagnosis, with the liver being one of the most common sites of metastasis. Infiltrative liver metastases are not amenable to optimal surgical removal; moreover, liver metastases are resistant to chemotherapy. Importantly, cancer cells interact with the immune microenvironment in metastatic organs to establish metastatic colonies. Specifically, macrophages are responsible for increased infiltration of cancer cells. Therefore, new forms of nano-immunotherapy can be utilized to target the interaction between macrophages and cancer cells. Conventional metastasis and cell invasion assays do not recapitulate the native primary or metastatic tumor microenvironments, and hence, do not predict drug efficacy very well. Decellularized liver biomatrices are an attractive alternative for in vitro drug screening to provide a more accurate 3D model of the metastatic microenvironment. Liver biomatrices were manufactured via sectioning and decellularization with a Triton X-100 and Ammonium Hydroxide detergent solution. The decellularized liver biomatrices were evaluated using scanning electron microscopy (SEM), DNA quantification, and histology to verify that the native cells had been successfully removed. Ovarian cancer cell (OVCAR 3) spheroids were then cultured with and without macrophages on hanging drop arrays and seeded onto the biomatrices to simulate metastasis. Samples were harvested at various time points in order to study the influence of macrophages on the invasive properties of metastatic ovarian cancer cells. Fixed biomatrices were imaged using scanning electron microscopy then analyzed with ImageJ software to quantify and compare ovarian cancer cell invasion across the different conditions. Preliminary SEM and histology data confirm adequate decellularization of the liver tissue. Therefore, the decellularized liver biomatrix can be used as a 3D model of the hepatic tumor microenvironment for the study of nano-immunotherapies for ovarian cancer liver metastasis (OCLM) as well as other forms of liver metastasis.
Citation
Farris, Heather A (2022). Decellularized Liver Biomatrices as a Model for 3D Cancer Metastasis. Undergraduate Research Scholars Program. Available electronically from https : / /hdl .handle .net /1969 .1 /200600.