Modelling adipose tissue-cancer crosstalk: a three-dimensional perspective

Figures

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  Fig. 1. Different types of adipose tissue. Adipose tissue is mainly divided into subcutaneous and visceral. Subcutaneous adipose tissue is found in the femoro-gluteal, dorsal, and ventral regions, while the visceral adipose tissue lines internal organs. At a cellular level, adipose tissue is composed of white, brown, and beige adipocytes, which display different morphologies and functions as determined by their intracellular content (lipid droplets and mitochondria). Their functions range from energy storage (white/beige adipocytes) to heat production and thermogenesis regulation (brown/beige adipocytes).

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  Fig. 2. Crosstalk between adipose tissue and cancer. A mutual influence between tumour cells and adipocytes is the core of the complex dynamics in the tumour and adipose tissue relationship. Cancer cells reprogramme adjacent cells such as adipocytes [85], immune cells (in blue and purple) [86], fibroblasts (in pink) [87], and endothelial cells (vessels in red) to support their proliferation [88] and induce lipolysis to fuel their own growth [62]. In turn, adipocytes release adipokines, hormones, cytokines, and FFAs to support tumour growth [4].

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  Fig. 3. Overview of 3D models of adipose tissue and cancer crosstalk. The figure depicts an overview of the 3D models employed by researchers to recapitulate the adipose tissue-cancer dynamics in vitro. Spheroids are aggregates of cells that self-organise in spherical structures when placed in appropriate physical conditions (i.e. low attachment vessel, hanging drop, agitation, microfluidics) [46]. Spheroids can be mono- or multi-cellular and formed with or without the addition of a structural protein or a mixture of them (i.e. collagen, Matrigel®). 3D scaffolds are structures that support the growth of cells, mimicking the natural extracellular matrix (ECM). The ECM has a fundamental role in providing physical and chemical signals to support cell growth and maintenance [50]. Scaffolds can be made of natural or synthetic polymers, and their structural properties can be tuned to adapt to specific applications. Organoids are self-organising 3D in vitro models that reproduce some of the hallmarks of real organs at a millimetre scale [89]. The specialised cell types (i.e. pluripotent stem cells, progenitor cells, mature cells) self-organise by forming structures that resemble full-scale…