Understanding the Influences of Hypoxic Oxygen Tumor Levels on Cell-Derived ECM — 15a — Karla Arcelay Garcia¹, Makarie Wiebersick¹, Hailey Axemaker¹, Pilar de la Puente^1,2,3

1   Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD 57104, USA

²   Department of Obstetrics and Gynecology, University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57105, USA

³   Department of Surgery, University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57105, USA

Ovarian cancer (OC) is amongst the most hypoxic tumor types and is the 5th leading cause of cancer deaths. OC is considered a severe disease which is characterized by the proliferation of tumorous cells in the ovaries, and it can manifest itself asymptomatically, making it difficult to identify in the earlier stages. An important contributor to OC is cancer associated fibroblast (CAFs), a type of cell within the tumor microenvironment that induces tumorigenic characteristics by extracellular matrix (ECM) remodeling and secretion of cytokines that can stimulate metastasis and proliferation of the cancer. This study uses cell-derived extracellular matrices (CD-ECMs) derived from CAFs of both uterine and ovarian origin and two OC cell lines (KURAMOCHI and SKOV-3) to investigate the potential effects of physoxia (7% oxygen) and hypoxia (1.5% oxygen) on the secretion and general homeostasis of the ECM by ascorbic supplementation. The cellularized ECM was characterized by using immunofluorescence staining. Ovarian cancer cells were added once CD-ECMs had been decellularized, allowing for examination of drug resistance, tumor progression, and cell attachment. As a result of these assays, we have identified that while laminin increased in hypoxia for both cell types, collagen and fibronectin had a tendency to increase in the SKOV-3 derived CAFs, but not in the KURAMOCHI derived CAFs when compared to physoxia. Hypoxia did not seem to change the attachment of cancer cells in the CD-ECMs of both cell lines when compared to physoxia. Tumor progression and drug resistance were enhanced in hypoxia compared to the physoxic values. In conclusion, our results suggest that hypoxia has a tendency to alter ECM remodeling but is cell type and origin specific. Therefore, understanding how OC progresses at different oxygen levels can help us develop early detection techniques and preventative strategies, which will ultimately improve results and survival rates.

Sanford Research
Dr. Pilar de la Puente