Featured Research

from universities, journals, and other organizations

Mechanical forces driving breast cancer lead to key molecular discovery

Date:
March 27, 2014
Source:
University of California, San Francisco (UCSF)
Summary:
The stiffening of breast tissue in breast-cancer development points to a new way to distinguish a type of breast cancer with a poor prognosis from a related, but often less deadly type, researchers have found in a new study. The findings may lead eventually to new treatment focused not only on molecular targets within cancerous cells, but also on mechanical properties of surrounding tissue, the researchers said.

The stiffening of breast tissue in breast-cancer development points to a new way to distinguish a type of breast cancer with a poor prognosis from a related, but often less deadly type, UC San Francisco researchers have found in a new study.

The findings, published online March 16, 2014 in Nature Medicine, may lead eventually to new treatment focused not only on molecular targets within cancerous cells, but also on mechanical properties of surrounding tissue, the researchers said.

In a mouse model of breast cancer, scientists led by Valerie Weaver, PhD, professor of surgery and anatomy and director of the Center for Bioengineering and Tissue Regeneration at UCSF, identified a biochemical chain of events leading to tumor progression. Significantly, this chain of events was triggered by stiffening of scaffolding tissue in the microscopic environment surrounding pre-cancerous cells. The stiffening led to the production of a molecule that can be measured in human breast cancer tissue, and which the researchers found was associated with worse clinical outcomes.

"This discovery of the molecular chain of events between tissue stiffening and spreading cancer may lead to new and more effective treatment strategies that target structural changes in breast cancers and other tumors," Weaver said.

In the mouse experiments, Janna Mouw, PhD, a UCSF associate specialist who works in Weaver's lab, found that tissue stiffening in microscopic scaffolding known as the extracellular matrix, or ECM, increases signaling by ECM-associated molecules, called integrins. The integrins in turn trigger a signaling cascade within cells that leads to the production of a tumor-promoting molecule called miR-18a.

Unlike most cellular signaling molecules thus far studied by scientists, miR-18a is not a protein or a hormone, but rather a microRNA, another type of molecule recognized in recent years to play an important role in the lives of cells. The miR-18a dials down the levels of a protective, tumor-suppressing protein called PTEN, which often is disabled in cancerous cells, leading to abnormal biochemical signaling that can promote cancer growth.

Stiffening of the Tissue Microenvironment in Tumors

Weaver is a trained biochemist, and has been a trailblazer in the study of tissue mechanics and cancer for 15 years. Mouw is a mechanical engineer. The newly reported UCSF discovery highlights the importance of mechanical forces in the development of cancer, which usually is thought of in biochemical terms.

Armed with modern lab techniques, Weaver has made many discoveries about the mechanical and structural properties of tumor tissue and the stiffening that can occur. For example, she was the first to identify the cross-linking of structural elements within the ECM as a precursor to cancer progression.

Her research team's latest findings are of clinical interest because they may lead to earlier identification of certain difficult-to-treat breast cancers. About 60 percent of breast cancers can be easily identified as a type known as luminal breast cancer, but there are two subtypes of luminal breast cancer that are difficult to distinguish.

Luminal A breast cancer accounts for about 40 percent of all breast cancers, while luminal B breast cancer comprises about 20 percent. On average, women with luminal B breast cancer do not survive as long after treatment without breast cancer recurring, and they are less likely to respond to hormone therapies such as tamoxifen. Lack of a good diagnostic tool results in overtreatment of many luminal A breast cancers, Weaver said.

According to Shelley Hwang, MD, PhD, chief of breast surgery at Duke University Hospital, former UCSF faculty member and a clinical collaborator for the Nature Medicine study, "Current methods for distinguishing luminal A breast cancer from luminal B breast cancer are expensive and time consuming, and are rarely used in medical practice." If a link between miR18a and luminal B breast cancer can be definitively confirmed, and if a reliable clinical laboratory test can be developed to measure miR18a in the tumor tissue, it would provide a practical way to distinguish the two tumor subtypes, Hwang said.

Laura Van't Veer, head of the breast oncology program at the Helen Diller Family Comprehensive Cancer Center at UCSF, and the developer of MammaPrint, a 70-gene test used to predict breast cancer spread, said the Nature Medicine study represents a major finding.

"The work provides early evidence that miR18a is a strong predictor of metastasis and poor survival in women with luminal breast tumors, and that it may be used to distinguish luminal A breast tumors from luminal B breast tumors," Van't Veer said.


Story Source:

The above story is based on materials provided by University of California, San Francisco (UCSF). The original article was written by Jeffrey Norris. Note: Materials may be edited for content and length.


Journal Reference:

  1. Janna K Mouw, Yoshihiro Yui, Laura Damiano, Russell O Bainer, Johnathon N Lakins, Irene Acerbi, Guanqing Ou, Amanda C Wijekoon, Kandice R Levental, Penney M Gilbert, E Shelley Hwang, Yunn-Yi Chen, Valerie M Weaver. Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nature Medicine, 2014; DOI: 10.1038/nm.3497

Cite This Page:

University of California, San Francisco (UCSF). "Mechanical forces driving breast cancer lead to key molecular discovery." ScienceDaily. ScienceDaily, 27 March 2014. <www.sciencedaily.com/releases/2014/03/140327165948.htm>.
University of California, San Francisco (UCSF). (2014, March 27). Mechanical forces driving breast cancer lead to key molecular discovery. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2014/03/140327165948.htm
University of California, San Francisco (UCSF). "Mechanical forces driving breast cancer lead to key molecular discovery." ScienceDaily. www.sciencedaily.com/releases/2014/03/140327165948.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
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