Researchers Find Clues in Obesity's Impact on Breast Cancer

A significant amount of research suggests that obesity advances the progression of breast cancer. Exactly why it has this effect, though, isn’t well understood. 

For their research, which combines laboratory experiments and computer simulations, a team of scientists from Yale and Cornell University aiming to better understand breast cancer has received a $2 million grant from the National Institutes of Health (NIH). 

Most breast cancers start in the epithelial lining of the milk duct. When it breaks out of the milk ducts, it enters the adipose tissue, a fatty connective tissue made up of cells known as adipocytes. The number of cancer cells that progress into the adipose tissue and whether they reach the vasculature in the adipose tissue are critical factors that determine how deadly the cancer is. 

Computer simulations of lipolysis during tumor cell invasion into adipose tissue

“If the cancer cells make it into a blood vessel, then there's the chance of metastasis, which yields a bad prognosis for the patient,” said Corey O’Hern, professor of mechanical engineering & materials science, physics, and applied physics.

Obesity has shown to be a significant factor in facilitating the process of cancer invasion. To understand why, most current research focuses on biochemical aspects of cancer. O’Hern, Valerie Horsley and their research teams, though, are focusing on how altered physical properties of the adipose tissue can affect cancer cell invasion.

“Adipose tissue that surrounds the mammary ducts can shrink and grow depending on a number of factors, yet how these fat cells in mammary tissue function is not well understood,” said Horsley, professor of molecular, cellular, and developmental biology and dermatology.

The adipocytes are larger than the cancer cells by at least a factor of 10. For obesity, the adipocytes swell to even larger sizes.

“So if the adipocytes swell and pack tightly during obesity, it would seem that cancer cells would not be able to move through the densely packed adipose tissue,” O’Hern said.                                                                                                     

But the researchers’ preliminary results show that when cancer cells interact with adipocytes in mouse models with high obesity, it causes enhanced lipolysis in which the adipocytes lose lipid and shrink. This shrinking allows for the creation of pathways for the cancer cells to move through into the adipose tissue.

“Lipolysis can 'feed' the tumor cells so they can grow faster, but it also shrinks the surrounding tissue, which will give the cancer cells a new environment to invade and metastasize,” Horsley said.

The interdisciplinary research team includes experts in several fields – cancer, the biology and mechanics of adipose tissue, computational simulations of soft matter and biological systems, advanced omics approaches, and breast oncology. Ultimately, the team aims to define the physical properties of adipose tissue in people with obesity that contribute to enhanced tumor invasion during breast cancer. In doing so, this research could lead the way to new and more effective treatments for breast cancer.