Identification of the paracrine MoleculAr Networks linking Obesity and pancreatic cancEr progression

Starting date
January 1, 2017
Duration (months)
12
Departments
Medicine
Managers or local contacts
Melisi Davide

Cancer and obesity are the two major epidemics of the 21th century [1].
Pancreatic cancer (PC) is the fourth leading cause of cancer-related mortality among adults [2].
The majority of patients are diagnosed with metastatic disease, thus the identification of the earliest
molecular events responsible for the metastatic dissemination of PC remains critical for early
diagnosis, prevention, and treatment interventions. Recent studies supports the model that metastasis
is an early event in pancreatic carcinogenesis and is associated with an early epithelial-tomesenchymal
transition (EMT) phenotype.
Obesity is one of the most serious public health problems worldwide [1]. Several epidemiological
studies demonstrated positive associations between obesity and cancer incidence [6-7]. In particular,
higher prediagnostic body mass index was associated with stage and decreased survival among
patients with PC, suggesting that chronic exposure to the consequences of obesity may be important
in affecting patient survival [10]. However, the underlying mechanistic basis linking adipocytes to
tumor initiating events remains largely elusive.
Preliminary evidences from our group indicated that secreted factors from differentiated adipocytes,
or adipokines, induce EMT in an experimental model of pancreatic carcinogenesis.
We hypothesize that paracrine factors secreted by adipocytes could be responsible for a
rapid progression and an early metastatic spread of cells in pancreatic preneoplastic lesions.
The results of our project could contribute to describe the networks of adipokines directly involved
in the effects of adipose tissue on cancer development and progression, thus shedding new light in a
research field that is still in its infancy. Most importantly, the adipokines identified in this study could
serve as novel biomarkers to select a risk population among obese subjects for screening and, thus,
early diagnosis of PC

Project participants

Davide Melisi
Associate Professor

Activities

Research facilities