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Breast Cancer Breakthrough
By Stanley Robert
Hobart Mercury
14 January 2006
A PUZZLING and devastating feature of many breast cancers that have been treated, apparently successfully, by chemotherapy is that they can redevelop months or even years later.
This observation has led researchers to postulate that there must be a pool of breast cancer stem cells, resistant to chemotherapy, lurking within the breast, that can subsequently regenerate a tumour.
Other studies, of normal breast tissue, suggest there must be a pool of mammary stem cells that mammary glands grow and develop from.
A team of Melbourne researchers has now discovered the elusive cells -- mammary stem cells.
They showed, in a series of fascinating experiments reported in last week's issue of the prestigious journal Nature, how those cells develop into mammary glands and how they can, in certain contexts, develop into breast tumours.
Using a sophisticated machine known as a fluorescence-activated cell sorter or FACS, the team purified a rare cell type, based on a unique combination of proteins present on their surface, from a pool of cells isolated from the mammary glands of normal mice.
To test if those cells were mammary stem cells, they transplanted single cells into the mammary fat pads, cleared of cells, of young virgin mice. The mammary fat pad develops into a functioning mammary gland in adult mice but, cleared of cells, fails to develop.
In the mice transplanted with a single one of those cells, a full mammary gland developed.
To show that those glands were entirely derived from the single transplanted cell, the researchers first engineered the cells with a living dye. Each of those cells and any of its daughter cells could then be selectively stained blue.
Staining of mammary glands that developed in those mice showed that all parts of the gland stained blue, indicating that the entire gland did indeed develop from a single seed cell.
Are these mammary glands operational? When those mice were made pregnant, all the normal changes in mammary tissue occurred -- the development of certain lobular structures and even the production of milk.
The experiments proved the researchers had isolated mammary stem cells capable of generating an entire functioning mammary gland. Now they wanted to see if those same cells produced breast tumours.
So they transplanted mammary stem cells into the breast region of mice bred to genetically resemble some women who are genetically predisposed to breast cancer. In those mice, the stem cells, judged by the blue staining, developed into tumours.
This research confirms for the first time what many had suspected. The very cells that give life, by generating functional mammary glands, can in the wrong context lead to potentially lethal breast cancers.
Future research might identify new ways to specifically treat breast tumours so the stem cells are removed and therefore cannot reinitiate a tumour. Whether or not entire mammary glands could be regrown from mammary stem cells in women is a question some researchers will surely try to answer.
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