Lorne special: Piecing together the breast cancer puzzle

Jane Visvader

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This feature appeared in the January/February 2010 issue of Australian Life Scientist. To subscribe to the magazine, go here.

Why do some cells in mature tissue or a tumour suddenly break away and initiate a spate of uncontrolled growth and spread into other tissues in a way that harms the whole organism? What are the hallmarks of such a cell that set it apart as a troublemaker? Can we use those marks to identify them, and even more importantly, to stop them before things get out of hand?

These questions underpin many efforts in cancer research worldwide. One such endeavour at the Walter and Eliza Hall Institute (WEHI) for Medical Research in Melbourne has contributed several pieces already to the giant puzzle that is cancer. Recently it found one more piece, although it was a piece that no-one expected to fit where it did, not even the researchers involved.

Jane Visvader’s team is leading this effort, the main focus of which is investigating those cells in breast tissue that are predisposed to becoming tumorigenic and those cells that are responsible for sustaining breast cancer. “To do that, we need to first have a very good grasp of the basic biology underlying normal breast development,” Visvader says.

Breast cancer is a very heterogeneous disease in terms of both what the cells look like and the genetic markers they express, with six distinct subtypes already classified based on gene expression profiling. Thus, isolating and classifying functionally distinct epithelial cell populations in the mammary gland will help to work out the steps and critical factors that govern the differentiation of stem cells and progression of intermediate cells to form the mature tissue hierarchy. Only then can the field really start to reliably define potential cells of origin in breast cancer based on established relationships between the normal cell subsets and tumor types, as well as the key cell changes that could underlie the observed breast cancer heterogeneity.

As part of this global push, WEHI’s Victorian Breast Cancer Research Consortium Laboratory, which Visvader co-heads with scientist and clinical oncologist, Associate Professor Geoff Lindeman, has spent many years systematically identifying and finding out as much as they can about the normal epithelial cells that reside in breast tissue from human and mouse. These sorts of basic studies are critical for the team’s long-term goal of identifying potential targets for breast cancer that may be useful as diagnostic or prognostic markers and for developing new therapeutic strategies.

In 2006, Visvader and Lindeman’s team reported the first identification of a mouse mammary stem cell. “Since then, we have made some progress identifying daughter progenitor cells that lie between the stem cells and the mature cells that make up mammary tissue,” says Visvader. At the same time, the group was also focussing on compiling the same sort of biological data in humans – this culminated in their recent publication in Nature Medicine of the mammary stem cell in normal human tissue.

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