Inflammation Related to Obesity in the Etiopathogenesis of Gastroenteropancreatic Neuroendocrine Neoplasms

Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare neoplasms, which, due to their heterogeneous nature, non-specific symptoms, and lack of specific tumor markers pose many diagnostic and clinical challenges. In recent years, the effectiveness of GEP-NEN diagnosis has increased, which is probably associated with the greater availability of diagnostic tests and the cooperation of many experienced specialists in various scientific disciplines. In addition to the possible genetic etiology, the cause of GEP-NET development is not fully understood. Inflammation and obesity are known risks that contribute to the development of many diseases. Chronic inflammation accompanying obesity affects the hormonal balance and cell proliferation and causes the impairment of the immune system function, leading to neoplastic transformation. This review explores the role of inflammation and obesity in GEP-NETs. The exact mechanisms inducing tumor growth are unknown; however, the profile of inflammatory factors released in the GEP-NET tumor microenvironment is responsible for the progression or inhibition of tumor growth. Both the excess of adipose tissue and the impaired function of the immune system affect not only the initiation of cancer but also reduce the comfort and lifetime of patients.

Keywords: adipokines; cytokines; gastroenteropancreatic neuroendocrine tumors; inflammation; neuroendocrine neoplasms; obesity.

Figure 1

Mechanisms of pro- and anti-carcinogenic activity of selected inflammatory factors. Abbreviations used: Akt (PKB): protein kinase B; COX2: cyclooxygenase 2; DISC: death-inducing signaling complex; EMT: epithelial–mesenchymal transition; IL-6: interleukin 6; IL-17: interleukin 17; IL-23: interleukin 23; IFN-γ: interferon-gamma; JNK: c-Jun N-terminal kinases; MAPK: mitogen-activated protein kinases; MMP9: matrix metallopeptidase 9; NF-кB: nuclear factor kappa B; PI3K: phosphatidilinositol 3-kinases; RNS: reactive nitrogen species; ROS: reactive oxygen species; Src (short from sarcoma): proto-oncogene tyrosine–protein kinase; STAT3: signal transducer and activator of transcription 3; TNF-α: tumor necrosis factor α. The upwards arrow indicates an increase in the parameter’s level; the downwards arrow indicates a decrease in the parameter’s level.

Figure 2

Relationship between obesity and gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Abbreviations used: 5-HIAA: 5-hydroxyindole acetic acid; AMPK: AMP-activated protein kinase; CgA: chromogranin A; IGF-1: insulin-like growth factor-1; mTOR: mammalian target of rapamycin kinase; NF-κB: nuclear factor kappa B; NSE: neuron-specific enolase. The upwards arrow indicates an increase in the parameter’s level; the downwards arrow indicates a decrease in the parameter’s level.