90: Obesity and Gastric Cancer Aggressiveness – a New Link

Friday, March 24, 2023

2:13 PM – 2:25 PM

Location: Veterans Memorial Auditorium

Author(s)

Shelly Loewenstein, PhD

Senior researcher
Tel-Aviv Sourasky Medical Center and Tel-Aviv University
Tel Aviv, Israel

Disclosure information not submitted.
AR

Adi Rubin, Msc

MSc Student, Surgical Oncology Research Laboratory
Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel, United States

Disclosure(s): No financial relationships to disclose

Abstract Presenter(s)

Guy Lahat, MD (he/him/his)

Head Surgery Division
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, Israel

Disclosure(s): No financial relationships to disclose

First Author(s)

AR

Adi Rubin, Msc

MSc Student, Surgical Oncology Research Laboratory
Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel, United States

Disclosure(s): No financial relationships to disclose

Author(s)

AF

Adi Friedman

Tel-Aviv Sourasky Medical Center

Disclosure information not submitted.
Eran Nizri, MD, PhD

Head of Unit
Tel-Aviv Sourasky Medical Center
Tel Aviv, Tel Aviv, Israel

Disclosure information not submitted.
NL

Nir Lubezky, MD

Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel

Disclosure information not submitted.

Disclosure(s):

Adi Rubin, Msc: No financial relationships to disclose

Guy Lahat, MD: No financial relationships to disclose

Introduction: Gastric cancer (GC) peritoneal metastases, especially within the omentum, represents advanced disease stage and poor prognosis. Adipocytes are active metabolic cells with dynamic cellular cargo that affect endocrine, inflammatory and cancerous responses. However, our understanding of the exact mechanisms by which adipocytes mediate these responses is still incomplete. Extracellular vesicles (EVs) represents one of the most relevant cell-to-cell communication mechanism among cells within the tumor microenvironment. Here, we characterized the crosstalk between GC cells and primary adipocytes from the omentum of lean and obese GC patients mediated by EVs.

Methods: We compared the incidence of omental metastases among patients with and without obesity using retrospective clinical data of GC patients. Primary adipocytes were prepared from the omentum of lean and obese GC patients. Adipocytes-EVs were isolated and characterized. Proliferation, migration, and invasion assays were used to evaluate the phenotypic behavior of treated GC cells. Tube formation assay was used to evaluate angiogenesis. The expression of epithelial to mesenchymal transition (EMT) associated transcripts in GC cells stimulated with adipocytes-EVs was evaluated using qRT-PCR. Finally, differentially expressed miRNA within lean and obese adipocytes-EVs were determined using NanoString technology.

Results: Initially, we demonstrate a positive corellation between BMI, visceral fat content and GC omental metastasis. We prepared primary adipocytes from the omentum of lean and obese GC patients, isolated, and characterized their secreted EVs. GC cells were stimulated with adipocytes-EVs. We show that obese adipocytes-EVs enhance the proliferation, migration and invasion of GC cells compared to lean adipocytes-EVs. In addition, we demonstrate that obese adipocytes-EVs promote angiogenesis in vitro. Next, we show that obese adipocytes-EVs induced the expression of EMT related genes, e.g. MMP13, Vimentin and ZEB1 and reduce the expression of E-cadherin in GC cells. Finally, we identified 80 differentially expressed miRNA within lean and obese adipocytes-EVs.

Conclusions: We demonstrate for the first time that EVs isolated from primary adipocytes from the omentum of obese GC patients promote GC growth and progression. We also demonstrate that these effects may be mediated by the transfer of miRNAs and the induction of EMT in GC cells. Taken together, our results suggest a new mechanism linking obesity and GC aggressiveness mediated by EVs.

Learning Objectives:

learn about extracellular vesicles
understand the effect of adipocytes EVs on GC growth and progression
understand the ling between obesity and GC