Navigation Links
Novel detection method unmasks circulating breast cancer cells
Date:12/11/2009

SAN ANTONIO - Circulating metastatic breast cancer cells can lose their epithelial receptors, a process that enables them to travel through the bloodstream undetected, according to research from The University of Texas M. D. Anderson Cancer Center.

The findings were presented today at the CTRC-AACR San Antonio Breast Cancer Symposium.

Levels of these circulating tumor cells (CTCs) - which are shed from a primary tumor or its metastases - have been used to monitor and tailor cancer therapy and to predict a patient's prognosis. CTCs that have undergone epithelial-mesenchymal transition (EMT), however, evade current detection methods and lose their traditional prognostic and therapeutic value. Those cancer cells also become more resistant to chemotherapy and radiation therapy. Finding a reliable method to detect these stealth breast cancer cells may reveal additional therapeutic targets that could help eradicate micrometastatic disease in patients with breast cancer or other epithelial tumors.

EMT and the Invasion-Metastasis Cascade

EMT is a process in which cancer cells undergo transdifferentiation (transformation into a different type of cell). "The carcinoma cells activate a transdifferentiation program in order to acquire the ability to execute the multiple steps necessary for the invasion-metastasis cascade," said the study's first author Michal Mego, M.D., Ph.D., formerly a fellow at M. D. Anderson. "During EMT, epithelial cells acquire a mesenchymal appearance with increased motility and invasiveness."

The researchers hypothesized that these changes render the EMT-CTCs undetectable by current detection assays, such as CellSearch (Veridex). The cells' acquired resistance to chemotherapy and radiotherapy also suggested that EMT-CTCs are tumor-initiating cells and are responsible for tumor dissemination. Moreover, the researchers had found subgroups of high-risk patients with brain metastases, triple receptor-negative disease, or inflammatory breast cancer whose blood tests did not reveal elevated levels of CTCs, further supporting their hypothesis.

Detecting CTCs Through EMT Gene Expression

The researchers then set out to develop a detection method that could identify EMT-CTCs in the peripheral blood of breast cancer patients. They took approximately 5 mL of peripheral blood from 27 patients ranging in age from 34 - 72 years, with a median age of 54. Sixteen of the women had metastatic disease, 19 had inflammatory breast cancer, and 12 had primary, non-inflammatory breast cancer.

"Using magnetic beads coated with monoclonal antibodies capable of capturing the majority of hematopoietic cells in peripheral blood, we obtained a fraction of cells enriched for CTCs," said Mego, who is now a scientist at the National Cancer Institute in the Slovak Republic. "Next we isolated RNA from these cells to detect genes that are involved in epithelial-mesenchymal transition, using molecular biology technology, such as the polymerase chain reaction."

Five EMT genes were identified: TWIST1, SNAIL1, SLUG, ZEB1, and FOXC2. At least one of these genes was over-expressed in 21 percent of the patients. Over-expression of EMT genes was more common among women with triple receptor-negative breast cancer than among those without this high-risk signature. The researchers found no correlation between EMT gene expression and CTC count as measured by CellSearch or the carcinoma-associated antigen known as Ep-CAM (epithelial cell adhesion molecule).

"We found that current CTC detection methods underestimate the most important subpopulation of CTCs involved in tumor dissemination-those with tumor-initiating properties," said James Reuben, Ph.D., professor in M. D. Anderson's Department of Hematopathology, the study's senior author. "A novel detection method such as ours that is capable of detecting CTCs after EMT could add important new prognostic information and could be useful for monitoring treatment efficacy in real time."

The M. D. Anderson and the Slovak National Cancer Institute teams have initiated a confirmatory study among patients with metastatic breast cancer, prostate cancer, or colon cancer. They also have initiated studies designed to identify therapeutic targets on EMT-CTCs. In addition to Mego and Reuben, other authors on the M. D. Anderson study include: Massimo Cristofanilli, M.D., Eleni Andreopoulou, M.D., and Summer Jackson, all of the Department of Breast Medical Oncology; Hui Gao, Ph.D. Changping Li, M.D., Sanda Tin, M.D. and Evan Cohen, all of the Department of Hematopathology; and Sendurai Mani, Ph.D., Department of Molecular Pathology.


'/>"/>

Contact: Laura Sussman
lsussman@mdanderson.org
713-745-2457
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

Related medicine news :

1. Turning metal black more than just a novelty
2. Engineers, doctors at UCLA develop novel material that could help fight arterial disease
3. Novel Technology in Treating Chronic Sinus Infections Available at Baptist
4. Novel K-anonymity algorithm safeguards access to data
5. Tulane Cancer Center to begin novel clinical trial for late-stage prostate cancer drug
6. Abbott to Acquire Novel Investigational Biologic to Treat Chronic Pain
7. Dallas Facial Plastic Surgeon Publishes Cutting-Edge Novel Approach To Facelift Technique
8. Porter Novelli Wins Gold from Medical Marketing & Media for Best Unbranded TV Ad
9. NeoVista Presents Interim Study Results of Novel Therapy for the Treatment of Neovascular Age-Related Macular Degeneration
10. Important new novel 2009 H1N1 flu advisory for cardiopulmonary transplantation
11. Possible Novel H1N1 Cases in Pigs Not Unexpected; Experts Say U.S. Pork Is Safe to Eat
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Apple ... care services, staged a mock evacuation of the facility as part of a disaster ... Fire Department, Echo Hose EMS and Shelton City Emergency Manager, as well as the ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Global Healthcare Management’s ... Alexandria Park in Milford, NJ. This free event, sponsored by Global Healthcare Management’s ... The fun run is geared towards children of all ages; it is a ...
(Date:10/13/2017)... ... October 13, 2017 , ... “The Journey: From the ... danger possible to save lost souls in the Philippines. “The Journey: From the Mountains ... a dedicated teacher of the Bible. She has taught all ages and currently teaches ...
(Date:10/12/2017)... ... October 12, 2017 , ... Planet Fitness, one of the largest and ... plans to open a flagship location in Covington, LA at 401 N. U.S. Highway ... store next to Office Depot in the Holiday Square shopping center. Its location allows ...
(Date:10/12/2017)... ... 2017 , ... Asante, a nationally recognized health system in ... existing home health joint venture through an agreement, effective October 1, 2017, to ... home health company with Asante, delivering clinically integrated care, for the past eight ...
Breaking Medicine News(10 mins):
(Date:10/10/2017)... -- NDS received FDA 510(k) clearance in May 2017 for its highly ... designed for endoscopy environments. An innovative secondary monitor solution, ZeroWire ... support the improvement of patient outcomes, procedural efficiency, and the lowering ... ... ...
(Date:10/4/2017)... 4, 2017  South Korean-based healthcare product Development Company ... "cprCUBE" on Kickstarter. The device will educate the user ... with better efficiency compared to the dated and pricey ... on efficacy of the compression for a more informed ... goal to raise $5,000. ...
(Date:10/2/2017)... 2017  Eli Lilly and Company (NYSE: ... third quarter of 2017 on Tuesday, October 24, 2017. ... day with the investment community and media to further ... call will begin at 9 a.m. Eastern time. Investors, ... webcast of the conference call through a link that ...
Breaking Medicine Technology: