Claudin-Low Subtype Tumor
The most recently identified tumor group is the claudin-low subtype. The subtype name is based on the defining feature of this group, specifically that these tumors exhibit low expression of many of the claudin genes, including 3, 4, and 7. The claudins are involved in epithelial cell tight–tight junctions. Another epithelial cell interaction protein is E-cadherin. These claudin-low tumors lack cell–cell junction proteins, including E-cadherin. The claudin-low tumors are also triple negative, and so can be considered another subtype of triple-negative disease, in addition to the basal-like group. As shown in the clustering analysis in Figure 7, claudin-low tumors are somewhat similar to basal-like cancers, but distinct (Fig. 7). Other important features of claudin-low tumors is that they almost always have an intense immune cell infiltrate, and they also have stem cell features and features of epithelial–mesenchymal transition (EMT).
Ovarian hormones awaken newly discovered breast stem cells
Walter and Eliza Hall Institute researchers have used advanced cellular, bioinformatics and imaging technology to reveal a long-lived type of stem cell in the breast that is responsible for the growth of the mammary glands during pregnancy.
The newly discovered stem cells, which respond to the 'ovarian hormones' progesterone and oestrogen, may also be linked to a high-risk form of breast cancer.
The discovery was made by Dr Nai Yang Fu, Dr Anne Rios, Professor Jane Visvader and Professor Geoff Lindeman as part of a 20-year research program into how the breast develops from stem cells, and how breast cancers can arise from stem cells and developing breast tissue. The research was published in Nature Cell Biology.
Dr Fu said the team had been able to build on their earlier discovery of breast stem cells, by defining subsets of stem cells with different functions, a project that was conducted in collaboration with bioinformatics researchers Dr Matthew Ritchie and Professor Gordon Smyth.
"When we looked at the genes that were switched on in these stem cells, we could distinguish subsets of stem cells that differed in their expression of genes encoding two proteins called Tetraspanin8 and Lgr5," he said. "By looking at the levels of Tetraspanin8 and Lgr5 protein on the surface of the cells, we could divide the stem cells into three separate groups."
The team used advanced technologies including three-dimensional imaging to show that the three groups of stem cells are located in different parts of the breast and function differently, Dr Rios said.
"We focused particularly on one stem cell subtype that had the highest levels of Tetraspanin8 and Lgr5 protein, which were located in the 'proximal' region of the breast around the nipple," Dr Rios said.
Professor Visvader said these stem cells were normally dormant - sitting quietly and not dividing - and remained in the proximal region throughout life. "However, when they were exposed to the hormones progesterone and oestrogen these cells awakened and could rapidly give rise to new breast cells," she said.
The research also revealed that the stem cells with high levels of Tetraspanin8 and Lgr5 protein had many similarities to a subtype of 'triple negative' breast cancers known as claudin-low cancers.