Triple positive cancer stem cells (CSCs) subtset of CTCs implicated in Metastasis

Key findings:

• A subset of CTCs occurring at low frequency are responsible for metastasis
• the frequency of occurrence in the reported study was 0 .6 to 33% of CTCs
• This subset is positive for CD44, CD47, MET 
• experimental method involved isolating CTCs from 350 breast cancer patients using cell surface markers and transplating them in mice with defective immune system
• As the disease advances, the number of triple-positive cells increases, but the total number of CTCs does not. 
• Patients with very high numbers of triple-positive cells had particularly high numbers of metastases and a much poorer prognosis than women in whom only few of these metastasis-inducing cells were detected

Conclusion: "On the whole, triple-positive cells seem to have a substantially higher biological relevance for disease progression than previously studied CTCs"

Metastasis stem cells in the blood of breast cancer patients discovered

direct link to the nature biotechnology paper
http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.2576.html

An Automated High-Throughput Counting Method for Screening Circulating Tumor Cells in Peripheral Blood - Analytical Chemistry (ACS Publications)

An Automated High-Throughput Counting Method for Screening Circulating Tumor Cells in Peripheral Blood - Analytical Chemistry (ACS Publications)

Summary:
This is a very unique paper that presents direct labelling of cells in whole blood. besides the traditional EpCAM, CD4-, CK markers, the authors also used CD44+ marker for stemness.

methods:
1 ml of blood directly stained with markers, centrifuged to remove excess labelling antibody and resuspended and flown through the microfluidic chip. A custom built line-confocal imaging system captures images of cells flowing past the microfluidic channel.
authors had previously published a variation of this technique here http://www.ncbi.nlm.nih.gov/pubmed/22389033

performance:

• 94% recovery 
• 1 ml of blood processed in ~ 30 mins
• no isolation/enrichment needed

interestingly, the performance of this system was compared with cellsearch in 90 clinical samples with the following findings

91% positive samples vs 44% positive using cellsearch in 7.5 ml of blood

range of cells 15 to 3375 per 7.5ml vs 1 to 846 by cellsearch

average 305 cells/ml vs 36 cells/ml by cellsearch

very impressive performance improvement over cellsearch.