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Review
. 2023 Nov 22;24(23):16589.
doi: 10.3390/ijms242316589.

Adipocyte Microenvironment in Ovarian Cancer: A Critical Contributor?

Ana Duarte Mendes  1 , Ana Rita Freitas  1 , Rodrigo Vicente  1 , Marina Vitorino  1 , Marta Vaz Batista  1   2 , Michelle Silva  1 , Sofia Braga  1   2   3
Affiliations
Review

Adipocyte Microenvironment in Ovarian Cancer: A Critical Contributor?

Ana Duarte Mendes et al. Int J Mol Sci. .

Abstract

Ovarian cancer is one of the most common gynecological malignancies and has low survival rates. One of the main determinants of this unfavorable prognosis is the high rate of peritoneal metastasis at diagnosis, closely related to its morbidity and mortality. The mechanism underlying peritoneal carcinomatosis is not clearly defined, but a clear preference for omental spread has been described. Growing evidence suggests that adipose tissue plays a role in promoting cancer onset and progression. Moreover, obesity can lead to changes in the original functions of adipocytes, resulting in metabolic and inflammatory changes in the adipose tissue microenvironment, potentially increasing the risk of tumor growth. However, the specific roles of adipocytes in ovarian cancer have not yet been fully elucidated. Due to the undeniable link between obesity and cancer, the adipose tissue microenvironment could also present a promising therapeutic target that warrants further research. This review discusses the complex relationship between ovarian cancer and the adipose tissue microenvironment.

Keywords: adipocyte; ovarian cancer; pathogenesis; peritoneal metastasis; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Main pathways regarding peritoneal metastasis. In ovarian cancer (OC), three steps are described as fundamental to the establishment of peritoneal metastasis. The first is an anatomical feature, the fact that there is an absence of an anatomical barrier protecting the ovary epithelium within the abdominal cavity. The second is that peritoneal fluid serves as a metastatic milieu for cell propagation through immune surveillance, resistance to anoikis, and the formation of spheroids. Finally, the modulation of the immune system in the tumor microenvironment (TME). The TME directly modulates the immune system in its favor through four steps: release of inflammatory cytokines, angiogenesis, the extensive and unregulated proliferation of extracellular matrix (ECM), and finally, angiogenesis to the benefit of neoplastic cells.
Figure 2
Figure 2
Interaction between ovarian cancer (OC) cells and adipose tissue (AT) within the tumor microenvironment (TME). The microenvironment within the peritoneal cavity is crucial for OC pathogenesis. The close collaboration between cancer cells, stromal cells, and adipocytes produces outcomes that flow in both directions. The stroma and AT play a vital role as a pre-metastatic niche, while cancer cells disrupt the normal adipose and stromal tissue, adapting it to their needs and creating an environment more conducive to cancer growth. Pro-inflammatory macrophages form a ring around dying and necrotic adipocytes (CAA—cancer-associated adipocytes), forming a crown-like structure (CLS). The development of cancer cells in the peritoneum tends to occur in the omental milky spots, lymphoid structures found in the omentum. CA125 and the overexpression of MMPs promote the adhesion of cancer cells into the peritoneal mesothelial layer. Afterward, the close interaction between CAA in the omentum and cancer cells stimulates tumor proliferation by various mechanisms: boosting a vast extracellular matrix (ECM), inducing a senescent-like phenotype, exchanging metabolites, and promoting immune regulation.
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This research received no external funding.