Spectroscopic imaging reveals early changes leading to breast tumours

Purdue University researchers have created a new imaging technology that reveals subtle changes in breast tissue, representing a potential tool to determine a woman's risk of developing breast cancer and to study ways of preventing the disease.
 
The researchers, using a special '3D culture' that mimics living mammary gland tissue, also showed that a fatty acid found in some foods influences this early pre-cancerous stage. Unlike conventional cell cultures, which are flat, the 3D cultures have the round shape of milk-producing glands and behave like real tissue, said Sophie Lelièvre, an associate professor of basic medical sciences.
 
Researchers are studying changes that take place in epithelial cells, which make up tissues and organs where 90 per cent of cancers occur. The changes in breast tissue are thought to be necessary for tumors to form, she said.

"By mimicking the early stage conducive to tumours and using a new imaging tool, our goal is to be able to measure this change and then take steps to prevent it," Lelièvre said.

The new imaging technique, called vibrational spectral microscopy, can be used to identify and track certain molecules by measuring their vibration with a laser. Whereas other imaging tools may take days to get results, the new method works at high speed, enabling researchers to measure changes in real time in live tissue, said Ji-Xin Cheng, an associate professor of biomedical engineering and chemistry.

By monitoring the same 3D culture before and after exposure to certain risk factors, the new method enables researchers to detect subtle changes in single live cells, he said.

Findings are detailed in a research paper that appeared in February in the Biophysical Journal. The paper was written by doctoral students Shuhua Yue, Juan Manuel Cárdenas-Mora, Lesley S Chaboub, Lelièvre and Cheng.
 
"This work shows the importance of engineering for the development of primary prevention research in breast cancer," said Yue, a biomedical engineering student whose work was funded through a fellowship from the US Department of Defense Breast Cancer Research Program.
The research is part of the International Breast Cancer and Nutrition (IBCN) project launched by Purdue in October 2010 to better understand the role nutrients and other environmental factors play in breast tissue alterations and cancer development.
 
Researchers studied live tissue in a culture that reproduces the mammary epithelium.
 
"This extremely sensitive technique shows the harmful impact of a nutrient called arachidonic acid," said Lelièvre, associate director of Discovery Groups at the Purdue Center for Cancer Research. "This fatty acid has been previously proposed to increase breast cancer risk, but until now there was no biological evidence of what it could do to alter breast epithelial cells."
 
The imaging method detects changes in the 'basoapical polarity' of epithelial tissues. Specific proteins and other biochemical compounds called lipids are normally located in one of two regions, called the basal and apical membranes. Because only certain proteins and lipids are found in basal membranes, while others are located only in apical membranes, the cells are said to be polarised.

"This polarity is critical for the proper structure and function of tissue," Lelièvre said. "What we have shown previously is that when polarity is altered, tissue that otherwise looks normal can be pushed into a cell cycle necessary to form a tumour. It's the earliest change in the epithelial tissue that puts the cells at risk to form a tumor. Now, thanks to the vibrational spectral microscopy technique developed by Dr Cheng, we can measure apical polarity status in live tissues and real time."