Volume 68, February 2023, 102322Author links open overlay panelAbstract

As one of the largest endocrine organs with a wide distribution in organisms, adipose tissue secretes multiple adipokines, cytokines, metabolites, and exosomes to promote tumour development. Elaborating the crosstalk between cancer cells and adipocytes provides a tissue-level perspective of cancer progression, which reflects the heterogeneity and complexity of human tumours. Three main types of adipose tissues, white, brown, and beige adipose tissue, have been described. Thermogenic capacity is a prominent characteristic of brown and beige adipocytes. Most studies so far mainly focus on the contribution of white adipocytes to the tumour microenvironment. However, the role of thermogenic adipose tissue in malignant cancer behaviour has been largely overlooked. Recently, emerging evidence suggests that beige/brown adipocytes play a key role in the development and progression of various cancers. This review focuses on the bidirectional communication between tumour cells and thermogenic adipocytes and the therapeutic strategies to disrupt this interaction.

Introduction

Tumour microenvironment (TME) refers to the environment in which a tumour originates and grows. The TME consists of cellular and acellular components that support tumour development, invasion, and metastasis. Metabolic reprogramming, a hallmark of tumours, can occur in cancer cells and the TME, and drive the malignant phenotype. Of note, obesity has become a global epidemic, and there is ample evidence of a link between obesity and increased cancer incidence, progression, and mortality [1]. It has long been known that adipose tissues (AT), including white adipose tissue (WAT), brown adipose tissue (BAT) and beige adipose tissue, play a vital role in energy metabolism and homeostasis under a non-tumour condition. Brown and beige adipocytes can promote energy expenditure, thermogenesis and insulin sensitivity to counteract hypothermia, obesity, and diabetes. However, the crosstalk between AT and tumours is less well defined. Certain cancer types, including cancer of the pancreas, oesophagus, stomach, lung, liver and bowel, are more commonly associated with cancer-associated cachexia (CAC) characterized by involuntary weight loss and BAT activation [2]. Recently, much interest has been generated with respect to the link between tumour cells and thermogenic adipocytes.

Section snippetsAT plasticity

AT can be broadly classified as WAT and BAT [3]. WAT, which is usually located beneath the skin (subcutaneous fat) and around internal organs (visceral fat), is mainly composed of white adipocytes containing a single large intracellular lipid droplet (LD), whereas BAT is located predominantly in the interscapular and supraclavicular regions of adult humans and is comprised of brown adipocytes with multiple small cytoplasmic LD. When dietary energy exceeds energy expenditure, surplus energy is

Phenotypic switching of adipocyte in cancer

Emerging evidence suggests that cancer should be considered a metabolic disease [10]. Tumour cells program their metabolism to support cancer progression, which may modify metabolic homeostasis in the organism. For example, the ability to overconsume glucose is an important characteristic of cancer cells. Therefore, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has been extensively used in the diagnosis of primary and metastatic malignant tumours. In

A role for thermogenic adipocyte in cancer

The recruitment of thermogenic fat has a beneficial role in combating obesity and metabolic dysfunction [38]. To date, most studies have explored the metabolic functions of white adipocytes in oncology. However, the contribution of beige/brown adipocytes to tumour progression requires further investigation. Pretreatment of breast cancer cells with brown adipocyte differentiation medium enhanced beige/brown adipocyte characteristics and promoted the growth of tumour xenografts, which may result

Thermogenic adipocyte and cancer treatment

Inhibition and modulation of browning, which is the central process in the positive-feedback loop between adipocytes and cancer cells, may be an effective curative option. For example, studies have suggested that the cyclooxygenase-2 inhibitor, SC236, can slow down the tumour growth rate by inhibiting the conversion of beige adipocytes in breast cancer [29]. In addition, our previous study demonstrated that thermogenic inhibitors (H89 or KT5720) exerted antitumour effects in animal models of

Conclusions

Adipocytes, as an important cellular component of TME, are involved in cancer progression. Diverse mechanisms participate in the activation of beige and brown adipocytes in patients with cancer. Recent progress in elaborating the tumour-adipocyte interplay provides novel insights into the association between tumour cells and adipocytes, which may act as an obstacle of therapeutic failure and recurrence of cancer. Understanding the precise mechanisms or mediators involved in the interaction

Author contribution

K.D., G.W., H.S., and D.G. equally contributed to the writing of the original draft and the making of the figures. J.L. and L.W. conceived and edited the manuscript. All authors have read and approved the final version of the manuscript.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgement

This work was supported by the National Natural Science Foundation of China (nos. 81730073 and 81872074 to L.W.); National Key R&D Program of China (nos. 2021YFA0804800 and 2018YFA0800600 to J.L.); National Natural Science Foundation of China (no. 8200032 to G.W.); Beijing Chao-Yang Hospital Golden Seeds Fundation (no. CYJZ202122 to H.S.).

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