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Classic and Novel Adipocytokines at the Intersection of Obesity and Cancer: Diagnostic and Therapeutic Strategies

  • Metabolism (M Dalamaga, Section Editor)
  • Published:
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Abstract

Purpose of Review

In this review, we investigate the role of classic and novel adipocytokines in cancer pathogenesis synopsizing the mechanisms underlying the association between adipocytokines and malignancy. Special emphasis is given on novel adipocytokines as new evidence is emerging regarding their entanglement in neoplastic development.

Recent Findings

Recent data have emphasized the role of the triad of overweight/obesity, insulin resistance and adipocytokines in cancer. In the setting of obesity, classic and novel adipocytokines present independent and joint effects on activation of major intracellular signaling pathways implicated in cell proliferation, expansion, survival, adhesion, invasion, and metastasis. Until now, more than 15 adipocytokines have been associated with cancer, and this list continues to expand. While the plethora of circulating pro-inflammatory adipocytokines, such as leptin, resistin, extracellular nicotinamide phosphoribosyl transferase, and chemerin are elevated in malignancies, some adipocytokines such as adiponectin and omentin-1 are generally decreased in cancers and are considered protective against carcinogenesis.

Summary

Elucidating the intertwining of inflammation, cellular bioenergetics, and adiposopathy is significant for the development of preventive, diagnostic, and therapeutic strategies against cancer. Novel more effective and safe adipocytokine-centered therapeutic interventions may pave the way for targeted oncotherapy.

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Abbreviations

AdipoR1/R2:

Adiponectin receptor 1/2

Akt:

v-Akt murine thymoma viral oncogene homolog

AMPK:

5’ AMP-activated protein kinase

BC:

Breast cancer

BMI:

Body mass index

CVD:

Cardiovascular disease

DM:

Diabetes mellitus

DNA:

Deoxyribonucleic acid

ER:

Estrogen receptor

ERK 1/2:

Extracellular signal-regulated kinase 1/2

GRP78:

Glucose-regulated protein 78

GTP:

Guanosine-5′-triphosphate

HIF-1a:

Hypoxia-inducible factor-1a

IL:

Interleukin

IGF:

Insulin-like growth factor

IRS:

Insulin receptor substrate

JAK:

Janus kinase

JNK:

Jun N-terminal kinase

MAPK:

Mitogen-activated protein kinase

LEPR:

Leptin receptor

LIFRα:

Leukemia inhibitory receptor alpha

MMP:

Matrix metalloproteinase

mTOR:

Mammalian target of rapamycin

NAD:

Nicotinamide adenine dinucleotide

Nampt:

Nicotinamide phosphoribosyl transferase

NF-κB:

Nuclear factor-κB

NSCLC:

Non-small cell lung carcinoma

OSM:

Oncostatin M

PBEF:

Pre-B cell colony-enhancing factor

PCOS:

Polycystic ovary syndrome

PI3K:

Phosphatidylinositol 3-kinase

PPAR:

Peroxisome proliferator-activated receptors

PR:

Progesterone receptor

RBP-4:

Retinol-binding protein

ROCK:

Rho-associated coiled coil-containing protein kinase

SNPs:

Single nucleotide polymorphisms

STAT:

Signal transducer and activator of transcription

STRA6:

Stimulated by retinoic acid 6

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

VCAM-1:

Vascular cellular adhesion molecule-1

VEGF:

Vascular endothelial growth factor

WHR:

Waist-to-hip ratio

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  1. Nikolaos Spyrou and Konstantinos I. Avgerinos contributed equally to the preparation of the manuscript.

Authors and Affiliations

  1. 251 Airforce General Hospital, Kanellopoulou 3, 11525, Athens, Greece

    Nikolaos Spyrou & Konstantinos I. Avgerinos

  2. Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA

    Christos S. Mantzoros

  3. Section of Endocrinology, VA Boston Healthcare System, Boston, MA, USA

    Christos S. Mantzoros

  4. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527, Athens, Greece

    Maria Dalamaga

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Spyrou, N., Avgerinos, K.I., Mantzoros, C.S. et al. Classic and Novel Adipocytokines at the Intersection of Obesity and Cancer: Diagnostic and Therapeutic Strategies. Curr Obes Rep 7, 260–275 (2018). https://doi.org/10.1007/s13679-018-0318-7

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