title: Esophageal adenocarcinoma and obesity: peritumoral adipose tissue plays a role in lymph node invasion.
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.
authors: Department of Medicine, Internal Medicine 3, Endocrine-Metabolic Laboratory, University of Padova, Padova, Italy.
authors: Elisabetta
authors: E
authors: Trevellin
authors: Surgical Oncology Unit, Veneto Oncological Institute (IOV-IRCCS), Padova, Italy.
authors: Marco
authors: M
authors: Scarpa
authors: Department of General Surgery and Odontoiatrics, University Hospital of Verona, Verona, Italy.
authors: Amedeo
authors: A
authors: Carraro
authors: Department of Cardiothoracic and Vascular Sciences, University of Padova, Padova, Italy.
authors: Francesca
authors: F
authors: Lunardi
authors: Surgical Oncology Unit, Veneto Oncological Institute (IOV-IRCCS), Padova, Italy.
authors: Andromachi
authors: A
authors: Kotsafti
authors: Department of Molecular Medicine, Normal Anatomy Unit, University of Padova, Padova, Italy.
authors: Andrea
authors: A
authors: Porzionato
authors: Surgical Oncology Unit, Veneto Oncological Institute (IOV-IRCCS), Padova, Italy.
authors: Luca
authors: L
authors: Saadeh
authors: Surgical Oncology Unit, Veneto Oncological Institute (IOV-IRCCS), Padova, Italy.
authors: Matteo
authors: M
authors: Cagol
authors: Surgical Oncology Unit, Veneto Oncological Institute (IOV-IRCCS), Padova, Italy.
authors: Rita
authors: R
authors: Alfieri
authors: Department of General Surgery and Odontoiatrics, University Hospital of Verona, Verona, Italy.
authors: Umberto
authors: U
authors: Tedeschi
authors: Department of Cardiothoracic and Vascular Sciences, University of Padova, Padova, Italy.
authors: Fiorella
authors: F
authors: Calabrese
authors: Surgical Oncology Unit, Veneto Oncological Institute (IOV-IRCCS), Padova, Italy.
authors: Carlo
authors: C
authors: Castoro
authors: Department of Medicine, Internal Medicine 3, Endocrine-Metabolic Laboratory, University of Padova, Padova, Italy.
authors: Roberto
authors: R
authors: Vettor
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D048429:Cell Size; D017077:Culture Media, Conditioned / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D004938:Esophageal Neoplasms / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D014407:Tumor Cells, Cultured; D000098853:Podoplanin
chemical_list: D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D017077:Culture Media, Conditioned; D020738:Leptin; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; C541116:ACTA2 protein, human; C513384:CDH1 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin
keywords: adipose tissue; esophageal adenocarcinoma; metastasis obesity; peritumoral microenvironment