Adipocyte-Based Cell Therapy in Oncology: The Role of Cancer-Associated Adipocytes and Their Reinterpretation as Delivery Platforms

Abstract

Cancer-associated adipocytes have functional roles in tumor development through secreted adipocyte-derived factors and exosomes and also through metabolic symbiosis, where the malignant cells take up the lactate, fatty acids and glutamine produced by the neighboring adipocytes. Recent research has demonstrated the value of adipocytes as cell-based delivery platforms for drugs (or prodrugs), nucleic acids or loaded nanoparticles for cancer therapy. This strategy takes advantage of the biocompatibility of the delivery system, its ability to locate the tumor site and also the predisposition of cancer cells to come in functional contact with the adipocytes from the tumor microenvironment for metabolic sustenance. Also, their exosomal content can be used in the context of cancer stem cell reprogramming or as a delivery vehicle for different cargos, like non-coding nucleic acids. Moreover, the process of adipocytes isolation, processing and charging is quite straightforward, with minimal economical expenses. The present review comprehensively presents the role of adipocytes in cancer (in the context of obese and non-obese individuals), the main methods for isolation and characterization and also the current therapeutic applications of these cells as delivery platforms in the oncology sector.

Cancer-associated adipocytes: emerging supporters in breast cancer

“…Besides, NADPH is a required electron donor for reductive steps in lipid synthesis, nucleotide metabolism, and maintenance of reduced glutathione (GSH) [ 69 ]. CAAs play a functional role in tumor development through secreted adipocyte-derived factors and exosomes, and through metabolic symbiosis, in which malignant cells absorb lactic acid, fatty acids, and glutamine produced by adjacent adipocytes [ 70 ]. Therefore, it might be inferred that the metabolic reprogramming of glutaminolysis induced by CAAs could promote BC cells to regulate the redox state in order to favor proliferation.…”

Lipid Profiling in Cancer Diagnosis with Hand-Held Ambient Mass Spectrometry Probes: Addressing the Late-Stage Performance Concerns

“…A high fat diet has been shown to alter lipid metabolism in cancer and influence the interplay between normal and cancer cells [108]. This relationship is exemplified elegantly by the crosstalk between adipose tissue (storage for dietary lipids [109]) and tumors [110], with cancer-associated adipocytes [111] providing adipose-derived lipids for cancer progression [112] and proliferation [113], with stipulated therapeutic potentials [114,115].…”

Overview of the molecular mechanisms contributing to the formation of cancer‑associated adipocytes (Review)

“…Third, adipocytes can be attracted to tumors and some cancer cells preferentially migrate to sites rich in adipose tissue, indicating the potential application of adipocytes as cell-based delivery platforms for drugs (or prodrugs), nanoparticles, or nucleic acids ( 129 ). However, in comparison, CAAs are more aggressive and in an active state, exhibiting increased expression of various inflammatory factors.…”