Abstract A093: Investigating alterations in metabolic profile of ovarian carcinoma associated mesenchymal stem cells

Abstract Ovarian cancer causes more deaths than any other gynecologic cancer. Although aerobic glycolysis has been a hallmark of cancer metabolism, it has been found that ovarian cancer (OvCa) cells are metabolically plastic, also utilizing oxidative phosphorylation (OXPHOS) as an active metabolic pathway for their rapid proliferation and metastasis. A growing body of evidence also shows that cancer cells not only reprogram their own metabolism but also metabolically remodel the tumor microenvironment to meet their ever-increasing energy demand. Our lab has previously demonstrated that OvCa cells epigenetically reprogram their resident tissue mesenchymal stromal/stem cells (MSCs) to develop a cancer-supportive phenotype. These cancer-associated mesenchymal stem cells (CA-MSCs) support OvCa progression through several mechanisms, including enhanced metastasis. Recent work by our lab showed these CA-MSCs enhance metastasis by donating their mitochondria to metabolically vulnerable OvCa cells and increasing OvCa cell OXPHOS. While we have demonstrated the impact of CA-MSC mitochondrial transfer to OvCa cells, what changes are happening in the CA-MSC that allow them to transfer mitochondria to OvCa cells is still unknown. Gene set enrichment analysis performed on RNA sequencing data comparing patient derived CA-MSCs to normal MSCs revealed that OXPHOS is one of the top enriched pathways in CA-MSCs. Furthermore, the cell mito stress test comparing mitochondrial respiratory profile of patient derived normal MSCs and CA-MSCs demonstrated that CA-MSCs have significantly increased mitochondrial respiratory capacity compared to normal MSCs. Uncovering the metabolic profile of ovarian CA-MSCs for the first time, our data demonstrates that ovarian cancer alter the metabolism of the CA-MSC towards OXPHOS. Our current studies are focused on understanding the role of enhanced CA-MSC OXPHOS in mitochondrial transfer to OvCa cells and OvCa metastasis. Citation Format: Roja Baruwal, Leonard G. Frisbie, Lan Coffman. Investigating alterations in metabolic profile of ovarian carcinoma associated mesenchymal stem cells abstract. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84 (5 Suppl₂): Abstract nr A093.