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.

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

CARRARO, Amedeo;TEDESCHI, UMBERTO;
2015-01-01

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.
2015
adipose tissue; esophageal adenocarcinoma; metastasis obesity; peritumoral microenvironment; Actins; Adenocarcinoma; Adipocytes; Adipose Tissue; Aged; Antigens, CD31; Cadherins; Cell Size; Culture Media, Conditioned; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Leptin; Lymphangiogenesis; Lymphatic Metastasis; Male; Membrane Glycoproteins; Middle Aged; Neovascularization, Pathologic; Obesity; RNA, Messenger; Receptors, Adiponectin; Signal Transduction; Tissue Culture Techniques; Tumor Cells, Cultured; Paracrine Communication
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/944579
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