CTCs and their central role in metastatic cascade, tumor dissemination and progression

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Circulating tumor cells (CTCs) can be detected from the peripheral blood of cancer patients, and are viewed as a unique “liquid biopsy” for cancer prognosis and diagnosis (1). Unlike other cancer biomarkers, CTCs represent a sampling of the patient’s primary tumor. Furthermore, CTCs play a crucial role in tumor dissemination and progression, and are widely recognized as a seed for metastasis (2).

Their prognostic value has been established 10 years ago by the Cell Search® system (Veridex, Raritan, NJ, USA) for metastatic colorectal, breast and prostate cancer (3). In addition to their prognostic power, the molecular characterization analysis of these CTCs can provide important insights into cancer biology. CTCs disseminate from primary tumors by undergoing phenotypic changes that allow the cells to penetrate blood vessels. To be able to disseminate and metastasize, CTCs must be able to perform epithelial-mesenchymal transition (EMT) (4). In this aspect, their survival and metastatic capacity could be correlated with a phenotype change into cancer stem cells which have been suggested to be the active source of metastatic spread in primary tumors.

CTCs are very rare and heterogeneous. Epithelial cell adhesion molecule (EpCAM)-based enrichment technique is one of the most common approaches for isolating CTCs. However, this technique may fail to detect CTC subpopulations that have undergone EMT (see our previous blog post). Recently, studies have suggested that EMT markers could be used for the detection or capture of CTCs (5). Some technologies, such as the AdnaTest technology, have been developed to assess phenotype changes like EMT and tumor stemness in CTCs, and help identify predictive biomarkers which can subsequently find their way into companion diagnostics (Visit: http://www.adnagen.com/).

The AdnaTest combines an immunomagnetic enrichment of CTCs followed by molecular profiling of the CTCs captured. What makes it unique is the use of a mix of antibodies directed against various tumor cell-associated antigens during the enrichment step. This addresses changes in the antigen profile of such cells in the circulation once they develop an EMT or tumor stem cell phenotype and, therefore, avoids missing such cells during enrichment. In the subsequent molecular profiling, several tumor-related genes are then analyzed in parallel to again deal with changes in the CTC metabolism due to their reaction to blood environment, drug influence or even general tumor variability.

Recently, I hosted a webinar titled “Circulating Tumor Cells: Seeds of Metastasation,” presented by Dr. Siegfried Hauch, Director of Liquid Biopsy and Site Manager at QIAGEN Hannover GmbH. Interested in the AdnaTest CTC Enrichment and Detection System? Watch Dr. Hauch’s recording to learn the technology and its applications in biomarker discovery. Click here to watch!

References

  1. 1. Molnar, B., Ladanyi, A., Tanko, L., Sréter, L. and Tulassay, Z. (2001) Circulating tumor cell clusters in the peripheral blood of colorectal cancer patients. Clin. Cancer Res. 7, 4080.
  2. 2. Baccelli, I. et al. (2013) Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat. Biotechnol. 31, 539.
  3. 3. Riethdorf, S. et al. (2007) Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin. Cancer Res. 13, 920.
  4. 4. Ksiazkiewicz, M., Markiewicz, A. and Zaczek, A.J. (2012) Epithelial-mesenchymal transition: a hallmark in metastasis formation linking circulating tumor cells and cancer stem cells. Pathobiology 79, 195.
  5. 5. Yu, M. et al. (2013) Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339, 580.

 

Wei Cao, Ph.D.

Senior Global Marketing Manager, Translational Sciences

Dr. Wei Cao joined QIAGEN in 2010 and currently leads the webinar program, presenting various topics on advanced techniques in biomedical research. She received her Ph.D. from Peking University in China in 2010, and conducted postdoctoral research at Weill Cornell Medical College in New York City. Before joining QIAGEN, Dr. Cao worked as a senior scientist in R&D in pharmaceutical and biotech, focusing on HIV, HCV and cancer drug discovery and development.

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