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Molecular interactions in obesity and cancer

Emma Allot, PhD Student
Emma Allot, PhD Student

The prevalence of obesity has increased markedly over the past two decades contributing to morbidity and mortality worldwide in the form of increasing rates of cardiovascular disease, diabetes and many types of cancer.  Mirroring the massive increase in obesity, the incidence of oesophageal adenocarcinoma in Ireland has doubled over the last 15 years and obesity has been identified as an independent risk factor for development of this cancer.

In addition, obesity has been linked to increased mortality following cancer development and therefore could contribute not only to increased cancer incidence but also to increased tumour progression.  A detailed investigation of the molecular mechanisms linking obesity and cancer is required. A recent study showed that abdominal obesity rather than body mass index (BMI) or general overweight is associated with oesophageal adenocarcinoma.  This suggests that the metabolic activity of abdominal fat (different to subcutaneous fat found directly underneath the skin) may play a role.

Oesophageal cancer is an aggressive disease associated with a poor five year survival of only 15 % (National Cancer Registry Ireland, 2000-2005) due in part to early lymphatic and haematogenous spread implying that pathways involved in tumour invasion and metastasis are of great significance.  The aim of this research project is to examine the molecular interactions between fat cells (adipocytes) and tumour cells in the context of oesophageal adenocarcinoma.  We want to establish if fat can fuel pathways to make a tumour more aggressive.

Our research group has established a fat biobank from patients undergoing surgery for oesophageal adenocarcinoma.  Following the patient’s consent two fat samples are collected during surgery, one from the abdominal cavity and one from directly underneath the skin (subcutaneous).  In the lab, differences in the fat from obese and non obese patients and from abdominal and subcutaneous sites are examined.  Fat tissue secretes metabolically active molecules called adipokines which could enhance the ability of the tumour to survive and grow in the body.  To investigate this, tumour cell lines grown in the lab are exposed to fat cells and/or fat derived molecules to determine their effect on tumour cells.  Some of our preliminary findings show that fat can increase tumour growth and movement, causing tumour cells to become more aggressive.  The next step is to determine the mechanisms by which fat can alter tumour cells in this way.

By furthering our knowledge of these critical biological mechanisms linking obesity and cancer we can pave the way for the development of novel therapeutic strategies and interventions to prevent and treat this disease.

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Last updated 23 November 2016 Surgery - Web Administrator (Email).