I recently read a press- release that very attractively used the term fly-paper to describe a novel invention by researchers at UCLA that can be used to grab maverick cancer cells circulating in the blood stream. These ‘mavericks’ I might add are known in Cancer jargon as Circulating Tumour Cells or CTCs. These tumour cells escape from an already formed tumour in the body and begin to circulate in the body via the bloodstream that involuntarily acts as a transport medium for these dangerous cells. The CTCs now form newer tumours in locations distinct from that of the original tumour, resulting in formation of ‘satellite tumours’ or colonies of tumour cells, giving rise to one of the most Distinctive and scaring features of a malignant tumour, namely, Metastasis.

A Cirulating Tumor Cell

A Cirulating Tumor Cell

The potential of a technology that can actually separate CTCs from the blood stream is tremendous, both in terms of Diagnosis and Cure of a malign cancer. If we can detect a CTC quickly, we can commence treatment quickly and hence, hope for a better prognosis. The technology used consists of a Silicon chip that has Nanopillars densely packed onto its surface. So it’s basically like a toothbrush…Imagine that the bristles are the nanopillars. These nanopillars are coated with anti-EpCAM, (epithelial cellular adhesion molecule) an antibody protein that can recognise and bind to Cancer cells. Efficacy testing was carried out by simply inserting the chip into the bloodstream along with a control chip that was flat (no nanopillars) but was nevertheless coated with the antibody in question. The chips were then withdrawn and stained using immunoflurescence techniques and then the numbers of CTCs in each of the test and control chips were counted.

The Fly- Paper

The Fly- Paper

The results were heartening, with the test chip managing to collect a whopping 45-65% of the CTCs as compared to the meagre 4-14% of the control or flat chip. The beauty of the invention, in my opinion was to play with the topography of the chip. Rather than simply coating a smooth (rounded or flat) surface with an anti-cancer antibody, the scientists increased surface area as well provided a kind of surface that had plenty of crevices, thus increasing the probability of a binding event between the CTCs and the antibodies.

In the observation of the lead researcher, Dr. Shutao Wang (a postdoctoral researcher at both the Crump Institute for Molecular Imaging at the David Geffen School of Medicine at UCLA and the California NanoSystems Institute at UCLA) the nano-size scale and the unique surface topography of the UCLA nanopillar chip may help it interact with nano-size components on cellular surfaces in the blood, enhancing capture efficiency.

Dr. Shutao Wang

Dr. Shutao Wang

The method can use existing lab equipments like cell incubators and automated immunoflurescence microscopes for detection of the CTCs. An added advantage is the detection time, where the current FDA approved CTC detection system, CellSearch, requires more than 3-4 hours for the process of detection; the nanopillars chip accomplishes it within 2 hours. The Veridex CellTrack Analyzer, which has been approved for use in monitoring therapeutic response in patients with breast, prostate and colon cancer, relies on the expression of EpCAM by epithelial cells and the isolation of these cells by immunomagnetic capture using anti-EpCAM antibodies.  Enriched CTCs are identified by immunoflurescence.

EpCAM- Antibody Staining

EpCAM- Antibody Staining

The technique is sure to revolutionize our response times to solid tumours and should result in better prognosis for the patient. However, I wonder whether the reliance of the technology on sufficient levels of EpCAM being expressed might prove to be a shortcoming.  I came across an abstract that mentioned the fact that, EpCAM has been reported to be down regulated in some cancerous cells. This might result in a lower efficiency of detection. Be that as it may, hats off to the researchers for further honing our ability to detect and fight this dreaded killer. Further studies will be aimed at detection in other samples such as urine, saliva or breast exudates and this Liquid biopsy is sure to make it simpler to detect cancerous cells.

REFERENCES:   Photograph Credits

1. www.scripps.edu/…/images/kuhn.CB.fig2.gif (CTC)

2. www.abcam.com/ps/datasheet/images/ab20160_1.jpg (EpCAM)

3. labs.pharmacology.ucla.edu/…/shutaoWang.jpg   (Dr. Shtuao wang)

4. http://www.nanotech-now.com/news.cgi?story_id=35448 (The Fly-Paper)

General References:

1.    http://www.nanotech-now.com/news.cgi?story_id=35448

2. http://www.biomarkerwebinars.com/BiomarkerSymposia_Content.aspx?id=88454 (Downregulation of EpCAM)

3. www.scripps.edu  (Complete Paper on alternative method of detection of CTCs)