Oncotarget

Research Papers:

Esophageal adenocarcinoma and obesity: peritumoral adipose tissue plays a role in lymph node invasion

Elisabetta Trevellin _, Marco Scarpa, Amedeo Carraro, Francesca Lunardi, Andromachi Kotsafti, Andrea Porzionato, Luca Saadeh, Matteo Cagol, Rita Alfieri, Umberto Tedeschi, Fiorella Calabrese, Carlo Castoro and Roberto Vettor

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Oncotarget. 2015; 6:11203-11215. https://doi.org/10.18632/oncotarget.3587

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Abstract

Elisabetta Trevellin1,*, Marco Scarpa2,*, Amedeo Carraro3, Francesca Lunardi4, Andromachi Kotsafti2, Andrea Porzionato5, Luca Saadeh2, Matteo Cagol2, Rita Alfieri2, Umberto Tedeschi3, Fiorella Calabrese4, Carlo Castoro2 and Roberto Vettor1

1 Department of Medicine, Internal Medicine 3, Endocrine-Metabolic Laboratory, University of Padova, Padova, Italy

2 Surgical Oncology Unit, Veneto Oncological Institute (IOV-IRCCS), Padova, Italy

3 Department of General Surgery and Odontoiatrics, University Hospital of Verona, Verona, Italy

4 Department of Cardiothoracic and Vascular Sciences, University of Padova, Padova, Italy

5 Department of Molecular Medicine, Normal Anatomy Unit, University of Padova, Padova, Italy

* These authors contributed equally to this work

Correspondence to:

Elisabetta Trevellin, email:

Keywords: Esophageal adenocarcinoma, adipose tissue, peritumoral microenvironment, metastasis obesity

Received: January 05, 2015 Accepted: February 19, 2015 Published: March 14, 2015

Abstract

Obesity is associated with cancer risk in esophageal adenocarcinoma (EAC). Adipose tissue directly stimulates tumor progression independently from body mass index (BMI), but the mechanisms are not fully understood. We studied the morphological, histological and molecular characteristics of peritumoral and distal adipose tissue of 60 patients with EAC, to investigate whether depot-specific differences affect tumor behavior. We observed that increased adipocyte size (a hallmark of obesity) was directly associated with leptin expression, angiogenesis (CD31) and lymphangiogenesis (podoplanin); however, these parameters were associated with nodal metastasis only in peritumoral but not distal adipose tissue of patients. We treated OE33 cells with conditioned media (CM) collected from cultured biopsies of adipose tissue and we observed increased mRNA levels of leptin and adiponectin receptors, as well as two key regulator genes of epithelial-to-mesenchymal transition (EMT): alpha-smooth muscle actin (α-SMA) and E-cadherin. This effect was greater in cells treated with CM from peritumoral adipose tissue of patients with nodal metastasis and was partially blunted by a leptin antagonist. Therefore, peritumoral adipose tissue may exert a direct effect on the progression of EAC by secreting depot-specific paracrine factors, and leptin is a key player in this crosstalk.


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