Stem cells from abdominal fat of obese women prompt breast cancer cells to proliferate. They accomplish this more efficiently than fat stem cells from non-obese women and fat stem cells from other body areas. The mechanism of action involves leptin, a potential drug target, according to new research from Tulane University published in a recent issue of Breast Cancer Research.
“The Tulane study certainly supports the link between obesity and breast cancer and begins to tease out the potential contribution of adipose (fat) stem cells via an estrogen/leptin axis,” says Jeffrey Karp, codirector of the Center for Regenerative Therapeutics at Brigham Women Hospital and a Harvard Stem Cell Institute principal faculty member who was not involved in the current work. “The study also hints at potential therapeutic targets to inhibit breast tumorigenesis, or tumor progression, although additional studies are required to test this.”
Bruce Bunnell, director of Tulane’s Center for Stem Cell Research and Regenerative Medicine, cocultured breast cancer cells with adipose-derived stem cells (ASCs) from 24 women. He found that when cocultured with ASCs from non-obese women, breast cancer cells did not proliferate faster. But when cocultured with ASCs from abdominal and nonabdominal areas of obese women, breast cancer cells proliferated faster.
Genetic analysis revealed that nonabdominal stem cells from obese women turned on 13 breast cancer related genes involved in metastasis, apoptosis and angiogenesis. But abdominal cells from obese women turned on those 13 genes—plus an additional 14 more, all cancer-related.
Bunnell’s group then placed ASCs and breast cancer cells from the same areas into the mammary fat pads of mice. The ASCs released leptin, but cancer cell growth was not affected. Only after an estrogen pellet was transplanted into the animals did the tumors grow across the board. And, as expected, tumors were largest when fed by ASCs from the abdominal areas of obese women.
The study suggests fat stem cells of obese women produce excess leptin. When a certain critical mass of leptin is achieved, after exposure to certain critical levels of estrogen, the leptin fuels breast cancer cell growth, Bunnell’s group reported. The group did not investigate estrogen sources, but did note that the adipose tissue of obese women generally contains higher estrogen levels. These findings offer an explanation at the cellular and molecular level for the numerous reports generated over the years that breast cancer incidence is higher in obese women.
Bunnell’s work makes sense to stem cell researchers. Both cancer cells, and the inflammation promoted by them, release growth factors that can attract a variety of stem cells.
Not only could the findings lead to new therapies that target leptin, but they could also have ramifications for women undergoing breast reconstruction. A reconstruction technique that involves the relocation of fat from stomach, to breast, may not prove optimal for obese women. Other patients may end up affected, as well. Right now, there are 107 clinical trials registered with the National Institutes of Health in which adipose-derived stem cells are administered for a variety of disorders.
“At the present time we do not know what frequency of the cells promote tumor growth,” notes Bunnell. “Sadly, we do not have a method to specifically identify that specific population. But we hope to find a way to isolate them. I don’t think all adipose tissue needs to be avoided, but it may be a cautionary note to physicians about using adipose tissue form morbidly obese patients.”
Adipose stem cells are mesenchymal stem cells found in adipose tissue. Depending on the microenvironment, they can differentiate into a variety of cells, including fat, cartilage and bone.
