Fat cells a suspect for endometrial cancer

Nov 27 2017

An underlying mechanism linking obesity with the development of endometrial cancer has, for the first time, been demonstrated by a Hunter Medical Research Institute research team.

Current statistics show that 57% of women who develop endometrial cancer are obese, yet it hasn’t been clear how or why fat cells drive this particular cancer more than other tumour types.

University of Newcastle scientist Associate Professor Pradeep Tanwar assembled multidisciplinary expertise in nutrition, gynaecology, oncology and basic sciences to solve different parts of the puzzle.

“Endometrial cancer is the most common gynaecological cancer and exhibits the strongest association with obesity,” Associate Professor Tanwar says. “As obesity figures continue to rise we risk it becoming a tsunami.

“We have identified a protein called VEGF that is released from fat cells [adipocytes] and crosstalks with endometrial cells. It activates a signalling pathway known as mTOR, causing an excessive proliferation of cells – and when you have too many cells, you have cancer.”

Professor Lisa Wood, an expert in the immunology of obesity, says the finding is significant as health services world-wide face a ‘globesity’ epidemic.

“It’s a health crisis causing so many disease risks, although the link to cancer hasn’t been so clear,” she says. “We’ve been gathering fat tissue samples collected during weight-loss surgery, which allows us to analyse the biochemical changes that occur when you carry excess weight.

“Pradeep’s laboratory team added these cells to tumour cells to investigate the interaction.”

Gynaecologist Pravin Nahar, from John Hunter Hospital, believes the study sets the stage for preventive measures: “By identifying their predisposition, women can be warned in advance and hopefully we can repurpose therapies that suppress the VEGF pathway,” he says.

Associate Professor Tanwar found increased fat levels had a direct correlation with elevated VEGF protein expression. “VEGF is a major driver for the growth of new blood vessels and plays a pivotal role in cell proliferation,” he adds. “We proved that in both patient samples and laboratory models.

“Now we have to look for drugs that can target VEGF and interrupt the communication cycle in order to maintain healthy uterine function in obese women.  We are also planning to examine how obesity prevention steps can be helpful in reducing the risk of endometrial cancer.”

The study has just been published in the American Association for Cancer Research journal Molecular Cancer Research. The team also comprised researcher Subhransu Sahoo, and oncologists Janine M. Lombard, Yvette Ius, Kenneth Jaaback, Rachel O'Sullivan from John Hunter Hospital and Calvary Mater Newcastle.