Targeting Cancer-Associated Adipocytes Against Ovarian Cancer Metastasis
Abstract
Ovarian cancer (OVCA) is often detected at a late stage when the cancer cells have already metastasized throughout the abdominal cavity. While surgery and carboplatin-based chemotherapy is the standard of care for OVCA patients, no specific therapy is available that targets the metastatic processes of OVCA. The omentum (a fatty tissue covering the bowel) is the principal site of OVCA metastasis. The most common type of fat cells, white adipocytes, are the major constituents of this tissue. These adipocytes help cancer spread by secreting substances that attract them to the omentum and then by providing them with lipids as a fuel source. Hence, the interactions between OVCA cells and adipocytes are important for early metastasis. While our laboratory and others have explored the effect of adipocytes on cancer cells, not much is known about the effect cancer cells have on adipocytes. In our preliminary experiments, we found that white adipocytes, in the presence of OVCA cells, can change into beige adipocytes, which are significantly different in gene expression and function. The presence of beige adipocytes in the cancerous omentum has not yet been confirmed, and the effect that this cell population has on cancer metastasis is not known. We hypothesize that these beige adipocytes help cancer cells establish metastatic lesions on the omentum and aid in the progression of the disease. Therefore, through this proposal, we plan to (1) determine the percent of beige adipocytes that are present in the cancerous omentums of OVCA patients, (2) understand how white adipocytes change into beige adipocytes, and finally (3) determine if the beige adipocytes support cancer cells in the colonization of the omentum. To identify and characterize the beige adipocyte population, we will use the Drop-seq method. This method allows us to identify all cell types present in a sample (in this case cancerous omentum) by analyzing gene expression patterns from single cells. Next, by using mass spectrometry-based approaches we plan to identify the bioactive factor/s that can convert adipocytes from white to beige. Last, we will use mouse models to determine whether the beige adipocytes support tumor growth. By elucidating the role of beige adipocytes in OVCA disease progression, we may be able to identify novel therapeutic targets for desperately needed OVCA treatments.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110376
Entities
People
- Abir Mukherjee
Organizations
- United States Army
- University of Chicago