Novel Micropatterned Substrate for Investigation of Ovarian Cancer Aggregate Formation and Response to Epigenetic Drug Therapy

Ovarian Cancer (OvCa) is the deadliest gynecological cancer, with 90% of mortality being a direct result of metastasis. At this late stage, ovarian cancer is more challenging to treat, with only approximately 20% of women at an advanced-stage surviving beyond 12 years after treatment. Tumorigenesis is complex, and the heterogeneity of most tumors further exacerbates attempts for developing therapeutics. Several factors play a role in the elucidation of processes, one of which is the cellular microenvironment. The current consensus in cancer research is that 3D microenvironments are needed to better mimic in vivo response of tumors to drugs. This study will evaluate the feasibility of using a novel micropatterned substrate that enables 3D microenvironments for in vitro investigations of OvCa. The substrate was created through technologies used in integrated circuit fabrication utilizing micropatterns of titanium diboride etched on a silicon wafer (Si-TiB2). TiB2 micropatterns on the Si background establish stiffness, roughness, wetness, and charge gradients to induce selective deposition of growth factors, enabling self-assembly of cells into 3D aggregates. OVCAR3 and SKOV3 cell lines were used in the absence/presence of pan-genome epigenetic drugs such as suberoylanilide hydroxamic acid (SAHA). The micropatterned substrate supported cell proliferation, migration, and aggregate formation while maintaining phenotype and viability. Treating aggregates with SAHA maintained cell viability but caused disaggregation of SKOV3 aggregates. The micropatterned substrate allows investigations of drug therapy for cancer treatment. Furthermore, results suggest that epigenetic treatments have potential use for OvCa treatment.