Leptin: A Heavyweight Player in Obesity-Related Cancers.

Obesity, defined as the abnormal or excessive expansion of white adipose tissue, has reached pandemic proportions and is recognized as an important health concern since it is a common root for several comorbidities, including malignancies. Indeed, the current knowledge of the white adipose tissue, which shifts its role from an energy storage tissue to an important endocrine and metabolic organ, has opened up new avenues for the discovery of obesity's effects on tumor biology. In this review, we will report the epidemiological studies concerning the strong impact of obesity in several types of cancer and describe the mechanisms underlying the heterotypic signals between cancer cell lines and adipocytes, with particular emphasis on inflammation, the insulin/IGF-1 axis, and adipokines.

CEBP-β and PLK1 as Potential Mediators of the Breast Cancer/Obesity Crosstalk: In Vitro and In Silico Analyses.

Over the last two decades, obesity has reached pandemic proportions in several countries, and expanding evidence is showing its contribution to several types of malignancies, including breast cancer (BC). The conditioned medium (CM) from mature adipocytes contains a complex of secretes that may mimic the obesity condition in studies on BC cell lines conducted in vitro. Here, we report a transcriptomic analysis on MCF-7 BC cells exposed to adipocyte-derived CM and focus on the predictive functional relevance that CM-affected pathways/processes and related biomarkers (BMs) may have in BC response to obesity.

Proteomic Profiling of Extracellular Vesicles Released by Leptin-Treated Breast Cancer Cells: A Potential Role in Cancer Metabolism.

Tumor extracellular vesicles (EVs), as endocytic vesicles able to transport nucleic acids, proteins, and metabolites in recipient cells, have been recognized fundamental mediators of cell-to-cell communication in breast cancer. The biogenesis and release of EVs are highly regulated processes and both the quantity of EVs and their molecular cargo might reflect the metabolic state of the producing cells. We recently demonstrated that the adipokine leptin, whose circulating levels correlate with adipose tissue expansion, is an inducer of EV release from breast cancer cells.

Obesity and endocrine therapy resistance in breast cancer: Mechanistic insights and perspectives.

The incidence of obesity, a recognized risk factor for various metabolic and chronic diseases, including numerous types of cancers, has risen dramatically over the recent decades worldwide. To date, convincing research in this area has painted a complex picture about the adverse impact of high body adiposity on breast cancer onset and progression. However, an emerging but overlooked issue of clinical significance is the limited efficacy of the conventional endocrine therapies with selective estrogen receptor modulators (SERMs) or degraders (SERDs) and aromatase inhibitors (AIs) in patients affected by breast cancer and obesity.

The Emerging Role of Extracellular Vesicles in Endocrine Resistant Breast Cancer.

Breast cancer is the most common solid malignancy diagnosed in females worldwide, and approximately 70% of these tumors express estrogen receptor α (ERα), the main biomarker of endocrine therapy. Unfortunately, despite the use of long-term anti-hormone adjuvant treatment, which has significantly reduced patient mortality, resistance to the endocrine treatments often develops, leading to disease recurrence and limiting clinical benefits. Emerging evidence indicates that extracellular vesicles (EVs), nanosized particles that are released by all cell types and responsible for local and systemic intercellular communications, might represent a newly identified mechanism underlying endocrine resistance.