Modulation of lipid metabolism in interacting visceral adipocytes and ovarian cancer cells

Abstract

Ovarian cancer (OvCa) is the 5th leading cause of cancer‐related deaths in women. The primary site of OvCa metastasis is the adipocyte (ADI)‐dominated omentum. A growing body of evidence supports metabolic dysregulation as a cancer hallmark. This research was aimed at investigating metabolic changes in interacting OvCa cells and ADIs. Human omental ADIs were plated on OvCa cells for coculture experiments and protein detection. Fatty acid (FA) oxidation was assessed by radioisotopic assay. FA binding protein 4 knockout (FABP4−/−) and wild‐type (WT) mice were inoculated with OvCa cells and sacrificed 10 weeks later. Human OvCa and omental metastatic tissues were utilized for IHC. Lipid accumulation and transfer, from ADIs into OvCa cells, were evident following coculture. FA oxidation was elevated in cocultured OvCa cells in a time‐dependent manner. Increased activated hormone‐sensitive lipase abundance in cocultured ADIs indicates upregulated lipolysis. FABP4 deficiency reduced tumor growth in FABP4−/− mice compared to WT mice. FABP4 was evident in OvCa cells at the ADI interface of omental metastasis but absent in the primary tumor. These results suggest ADIs promote OvCa metastasis and alter metabolic activity. FABP4 may mediate trafficking of FAs, providing energy for OvCa survival and metastasis. These findings may identify novel therapeutic targets for OvCa treatment. Support: NIH‐NCI T32 CA 9594‐21.

Clinical outcomes of immunohistochemistry of the p53 Staining pattern in high-grade serous ovarian carcinoma

“…According to a previous review [24], most HGSOCs are usually diagnosed at an advanced stage and have a poor prognosis, similar to our study. Nieman et al [25] showed that 80% of patients with HGSOC presented with omental metastasis, similar to our study, which demonstrated that 83.3% of patients with HGSOC had omental metastasis. In addition, we found that omental metastasis was a significant pathological factor for predicting the p53 overexpression pattern in HGSOC (87.8% vs.…”

Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells

“…Secreted factors from the omentum have been shown to act as chemotactic factors that attract OC cells to this organ. Upon arrival, omental adipocytes have been shown to modulate OC cancer proliferation, metabolism, and response to chemotherapy (9,66,67). Given that OC mostly metastasizes via the trans-coelomic route and is mainly contained within the peritoneal cavity, the demonstration that adipose-derived exosomal miRNA can modulate epigenetic regulators in OC cells show that these cancer cells do not need to be in direct contact with adipocytes and can be located anywhere in the peritoneal cavity to be re-programmed by this microenvironment.…”

“…Adipose tissue is a central component of the cancer microenvironment (4), and is made up mostly of adipocytes and to a lesser extent, endothelial cells, and macrophages (5). Factors secreted by adipocytes as well as direct adipocyte-cancer cell interaction have been shown to support tumor progression in various cancer types including, breast, ovarian, prostate, and colon cancers (6)(7)(8)(9)(10).…”

Patient-derived functional immuno-oncology platform identifies responders to ATR inhibitor and immunotherapy combinations in ovarian cancer

“…High-grade serous ovarian carcinoma is the most common subtype of ovarian cancer, often diagnosed at an advanced stage with 10-year survival of 15% (1). Nearly 80% of the HGSC metastasize to omentum, a large fat tissue covering stomach and intestine, which provides metabolic and inflammatory microenvironment for cancer and immune cells (2). The standard of care for HGSC includes primary debulking surgery followed by platinum-based chemotherapy.…”