Cancer stem cells are rare cells found in some cancers and are thought to be responsible for their growth and spread. The role of cancer stem cells in initiating tumours is controversial and there is a great deal of interest in this concept worldwide.
It is important to identify and define the properties of cancer stem cells in common tumours because they are not killed by chemotherapy or radiation treatments and they may be responsible for resistance to these treatments. It is hoped that such knowledge will enable the design of new treatments targeting cancer stem cells but not normal stem cells, which are needed for tissue function.
We study Endometrial Cancer, the fourth most common cancer in women and the most common gynaecological cancer, accounting for 3% of cancer deaths in Western women.
Endometrial cancer is increasing in incidence due to the obesity epidemic. The goals of this project are to determine whether cancer stem cells are present in human endometrial cancer (of the uterine lining) and then to identify specific markers that will enable us to isolate and characterise them, and compare their properties with normal human endometrial (uterine lining) epithelial progenitor cells.
Ultimately we would like to compare them with cancer stem cells in other human cancers. Using our stem cell assays for identifying normal endometrial epithelial progenitor cells, we found a small number of cells in human endometrial cancer tissues that express stem cell genes and have key stem cell properties – clonogenicity and self-renewal.
When small numbers of tumour cells were transplanted into mice lacking an immune system, we grew tumours identical to the patients' original cancer. We are now working on identifying markers to separate endometrial cancer stem cells from the rest of the cancer cells.
We screened endometrial cancer cells and normal endometrial epithelial cells with a panel of 32 marker antibodies and identified those that were reactive. We are now testing the ability of our short-listed markers to identify endometrial epithelial progenitors and endometrial cancer stem cells.
One marker looks very promising for identifying the epithelial progenitor cells in one of our stem cell assays. Another marker we tried for the cancer stem cells looks less promising telling us how important it is to test whether the cells carrying a marker actually functions as stem cells. We are now trying the second marker on the priority list.
Dr Caroline Gargett
Cancer Council Research Grant
$100,000 in 2008, $93,500 in 2009, $93,500 in 2010