Featured Research

from universities, journals, and other organizations

Transition in cell type parallels treatment response, disease progression in breast cancer

Date:
January 31, 2013
Source:
Massachusetts General Hospital
Summary:
A process that normally occurs in developing embryos -- the changing of one basic cell type into another -- has also been suspected of playing a role in cancer metastasis. Now a study has associated this process, called epithelial-mesenchymal transition or EMT, with disease progression and treatment response in breast cancer patients. The report also identifies underlying mechanisms that someday may become therapeutic targets.

A process that normally occurs in developing embryos -- the changing of one basic cell type into another -- has also been suspected of playing a role in cancer metastasis. Now a study from Massachusetts General Hospital (MGH) Cancer Center researchers has associated this process, called epithelial-mesenchymal transition or EMT, with disease progression and treatment response in breast cancer patients. The report also identifies underlying mechanisms that someday may become therapeutic targets.

"Until now, EMT had only been modeled in experimental systems, but its clinical relevance was uncertain. Now we show that it can be detected in samples from breast cancer patients and that the tumor cells oscillate between these two states" says Shyamala Maheswaran, PhD, of the MGH Cancer Center, co-corresponding author of the report in the Feb. 1 issue of Science. "We find that the EMT state of breast cancer cells evolves in response to therapy and to disease recurrence, pointing to involvement of this mechanism in tumor spread and invasiveness."

Epithelial tissues line most bodily surfaces and cavities, and epithelial cells closely adhere to each other. During development, some epithelial cells develop traits of mesenchymal cells, including the ability to migrate to other parts of the embryo, establish themselves and develop into organs or other types of tissue. Several studies have suggested that a transition from epithelial to mesenchymal cell type is also involved with cancer metastasis, which involves tumor cells' migration to and invasion of other sites in the body, but identifying EMT stages of tissues has been challenging.

The MGH investigators developed a new assay that determines EMT stage by screening tumor samples for seven epithelial markers and three mesenchymal markers. In primary tumor samples from several breast cancer patients -- including samples of estrogen-receptor/progesterone-receptor-positive, HER2-positive and triple-negative tumors -- the assay revealed a small number of epithelial cells that also expressed mesenchymal markers. The investigators then conducted EMT analysis of circulating tumors cells (CTCs) -- cells that break off from solid tumors and travel through the bloodstream -- using the second-generation CTC-chip device developed in collaboration with the MGH Center for Engineering in Medicine.

Analysis of blood samples from 41 patients with metastatic breast cancer at various stages of their treatment identified CTCs expressing mesenchymal markers (M+) in samples from 16 patients. Pre- and post-treatment samples were available from 10 patients, 5 who had responded to treatment and 5 who had not. While post-treatment samples from patients whose tumors responded showed either an overall drop in the number of CTCs captured or fewer M+ cells, samples from patients whose tumors did not respond showed an increased proportion of M+ CTCs.

The investigators had access to serial blood samples taken from one patient at various stages during the course of her disease, which included initial response to an experimental treatment, followed by treatment resistance, subsequent response to another protocol and then resumed tumor progression. Both the number of CTCs and the proportion of cells with mesenchymal markers to those with epithelial markers dropped when her tumor responded to treatment and then rose when the disease progressed. The researchers also observed that an increase in M+ CTCs in this patient was associated with the appearance of multicellular clusters of CTCs, which conflicts with the predominant model of EMT inducing single tumor cells to migrate into the bloodstream, and they found evidence that the growth factor TGF-beta may mediate EMT in cancer.

"This study provides us with a new biologic understanding of breast cancer invasion and metastasis," says Daniel Haber, MD, PhD, director of the MGH Cancer Center and co-corresponding author of the Science paper. "Our ultimate goal is to find ways to prevent the metastatic spread of cancer, so understanding whether and how EMT plays a role is key towards reaching that goal. Extending these studies to more patients and to other types of cancer will help us understand more completely how EMT is induced in cancer and whether there are ways to prevent it." A Howard Hughes Medical Institute investigator, Haber is the Isselbacher/Schwartz Professor of Oncology at Harvard Medical School, where Maheswaran is an associate professor of Surgery.

Haber adds that this investigation would not have been possible without the availability of the CTC chip, which the MGH team is developing through a grant from Stand Up to Cancer. The study was also supported by the Breast Cancer Research Foundation, Susan G. Komen for the Cure grant KG090412, National Institute for Biomedical Imaging and Bioengineering grant EB008047, National Cancer Institute grant CA129933 the NCI-MGH Federal Share Program and the Howard Hughes Medical Institute.

Co-lead authors of the Science paper are Min Yu, MD, PhD, and Aditya Bardia, MB BS, of the MGH Cancer Center. Additional co-authors are Ben Wittner, PhD, Shannon Stott, PhD, Malgorzata Smas, David Ting, MD, Steven Isakoff, MD, PhD, Jordan Ciciliano, Marissa Wells, Kyle Concannon, Maria Donaldson, Lecia Sequist, MD, Elena Brachtel, MD, Dennis Sgroi, MD, Jose Baselga, MD, and Sridhar Ramaswamy, MD, MGH Cancer Center; and Ajay Shah and Mehmet Toner, PhD, MGH Center for Bioengineering in Medicine.


Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. Yu, A. Bardia, B. S. Wittner, S. L. Stott, M. E. Smas, D. T. Ting, S. J. Isakoff, J. C. Ciciliano, M. N. Wells, A. M. Shah, K. F. Concannon, M. C. Donaldson, L. V. Sequist, E. Brachtel, D. Sgroi, J. Baselga, S. Ramaswamy, M. Toner, D. A. Haber, S. Maheswaran. Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition. Science, 2013; 339 (6119): 580 DOI: 10.1126/science.1228522

Cite This Page:

Massachusetts General Hospital. "Transition in cell type parallels treatment response, disease progression in breast cancer." ScienceDaily. ScienceDaily, 31 January 2013. <www.sciencedaily.com/releases/2013/01/130131144341.htm>.
Massachusetts General Hospital. (2013, January 31). Transition in cell type parallels treatment response, disease progression in breast cancer. ScienceDaily. Retrieved September 18, 2014 from www.sciencedaily.com/releases/2013/01/130131144341.htm
Massachusetts General Hospital. "Transition in cell type parallels treatment response, disease progression in breast cancer." ScienceDaily. www.sciencedaily.com/releases/2013/01/130131144341.htm (accessed September 18, 2014).

Share This



More Health & Medicine News

Thursday, September 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Artificial Sweetener Could Promote Diabetes

Artificial Sweetener Could Promote Diabetes

Newsy (Sep. 17, 2014) Doctors once thought artificial sweeteners lacked the health risks of sugar, but a new study says they can impact blood sugar levels the same way. Video provided by Newsy
Powered by NewsLook.com
Ebola Vaccine Trial Gets Underway at Oxford University

Ebola Vaccine Trial Gets Underway at Oxford University

AFP (Sep. 17, 2014) A healthy British volunteer is to become the first person to receive a new vaccine for the Ebola virus after US President Barack Obama called for action against the epidemic and warned it was "spiralling out of control." Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Obesity Rates Steady Even As Americans' Waistlines Expand

Obesity Rates Steady Even As Americans' Waistlines Expand

Newsy (Sep. 17, 2014) Researchers are puzzled as to why obesity rates remain relatively stable as average waistlines continue to expand. Video provided by Newsy
Powered by NewsLook.com
President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins