Featured Research

from universities, journals, and other organizations

How breast cell communities organize into breast tissue

Date:
March 18, 2011
Source:
DOE/Lawrence Berkeley National Laboratory
Summary:
A new study has shown how communities of different types of breast cells self-organize into breast tissue. This work helps explain how the processes of stem cell differentiation and tissue architecture maintenance are coordinated, and might lead to a better understanding of what goes wrong in cancer.

These image show the distribution of cell lineages in human mammary epitheial cells over time in the presence of (top) an anti--E-cadherin agent and (bottom) an anti--P-cadherin agent. LEPs are stained green, and MEPs are stained red. (Image from Mark LaBarge)
Credit: Image from Mark LaBarge

In biology, the key to a healthy life is organization. Cells that properly organize themselves into communities live long and prosper, whereas disorganized cells can become cancerous. A study by researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) of the different types of cells that make up the human breast shows that not only do cells possess an innate ability to self-organize into communities, but these communities of different types of cells can also organize themselves with respect to one another to form and maintain healthy tissue.

Related Articles


Understanding this ability of different types of cell communities to self-organize into tissue may help explain how the processes of stem cell differentiation and tissue architecture maintenance are coordinated. It might also lead to a better understanding of what goes wrong in cancer.

Mark LaBarge, a cell and molecular biologist in Berkeley Lab's Life Sciences Division, and Mina Bissell, a Berkeley Lab Distinguished Scientist also with the Life Sciences Division, carried out a unique study of normal human mammary epithelial cells that had been enriched into pools of the two principal lineages that make up breast tissue -- the milk-producing luminals and the myoepithelials that blanket them. In healthy breast tissue, these two lineages organize themselves into an ordered bi-layer. To observe and quantify changes in the distribution of these cell lines with respect to one another over time, LaBarge, Bissell and a team of collaborators used a unique "micropatterning" technique, in which the cells were confined to a three-dimensional cylindrical geometry.

"We demonstrated that while bi-layered organization in mammary epithelium is driven mainly by the lineage-specific differential expression of the E-cadherin adhesion protein, the expression of the P-cadherin adhesion protein makes additional contributions that are specific to the organization of the myoepithelial layer," LaBarge says. "Disruption of these adherens junction proteins or the actomyosin network that supports them either prevented the formation of the bi-layer, or caused a loss of pre-formed bi-layers. This is the first reported evidence that the two principle lineages of adult human mammary gland possess intrinsic and reversible characteristics that guide their organization into a bi-layer."

Throughout a person's life, the various tissues in his or her body will be replenished and repaired by drawing upon a reservoir of adult stem cells. As new cells replace old ones or are used to construct new tissue, the architecture of that specific tissue must be maintained. Otherwise, cancer or other diseases can arise. This process requires that lineage-specific progenitor cells or their differentiated progeny be able to reach their ultimate destination within the tissue. This task is particularly daunting for breast cell lineages because the mammary gland undergoes cyclical changes in its architectural structure, showing as much as a 10-fold expansion in preparation for lactation followed by return to normal size. During these cycles, the precise bi-layered branching organization throughout the gland, in which a layer of secretory luminal epithelial cells (LEPs) is surrounded by a layer of contractile myoepithelial cells (MEPs), must be maintained.

"We hypothesized that mammary epithelial cells possess lineage-specific intrinsic abilities to self-organize into domains of lineage specificity, which would help explain how, for instance, the mammary stem cell-enriched zone in the ducts is maintained separately from the rank-and-file LEPs and MEPs, and how LEPs and MEPs form and maintain bi-layers," LaBarge says. "The phenomenon of self-organization has not been well studied in humans, perhaps because of the challenges of working with primary materials and a paucity of tractable culture systems for maintaining cell types from normal adult tissues."

Initially, LaBarge, Bissell and their collaborators used a classical self-organization assay, in which heterogeneous aggregates of dissociated cells from embryonic tissues were cultured on non-adherent agarose-coated surfaces, to observe organization amongst cells divided into low and high cadherin expression groups. While somewhat effective, there was a "tremendous variation" in the size and shape of the aggregations of cells that, among other factors, made watching the same cells over time "out of the question," according to LaBarge. To meet this challenge, he and his colleagues engineered a microwell culture platform that could confine mixtures of human mammary epithelial cells to a 3D cylindrical geometry.

"Suddenly, we could work with small numbers of rare cells and we could watch them in action over time and perturb the system in meaningful ways," LaBarge says, "which could all be quantified and displayed in an unbiased manner."

In addition to the micropatterned assays, LaBarge and Bissell also made use of a cell culture system invented by Martha Stampfer and Jim Garbe, both with Berkeley Lab's Life Sciences Division. This unique cell culture system made it possible for LaBarge and Bissell to carry out their study using normal human adult epithelia.

"Without the Stampfer and Garbe system, our experiments would likely have been one-offs that were subject to the genetic makeup of the host," LaBarge says. "Instead, we were able to perform the experiments many times on the same lot of isogenic LEPs and MEPs to arrive at statistically significant conclusions."

LaBarge says the discovery of the important roles played by E-cadherin and P-cadherin proteins in the organization of human LEPs and MEPs into a bi-layer was a major surprise.

"For the formation of the breast tissue bi-layer, the LEP and MEP progenitor cells need a way to get instructions, or else the differentiated LEP and MEP cells need to find their correct home," he says. "Modulation of LEP and MEP activity seems to get the cells to where they ultimately need to be, but, as other studies have suggested, there is clearly much more to maintaining a breast tissue bi-layer than just adherens like LEP and MEP."

LaBarge and Bissell reported these findings in a paper published in the Proceedings of the National Academy of Science.

This research was supported in part by a grant from the National Cancer Institute, and by Berkeley Lab's Laboratory Directed Research and Development (LDRD) funding program.


Story Source:

The above story is based on materials provided by DOE/Lawrence Berkeley National Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. L. Chanson, D. Brownfield, J. C. Garbe, I. Kuhn, M. R. Stampfer, M. J. Bissell, M. A. LaBarge. Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells. Proceedings of the National Academy of Sciences, 2011; 108 (8): 3264 DOI: 10.1073/pnas.1019556108

Cite This Page:

DOE/Lawrence Berkeley National Laboratory. "How breast cell communities organize into breast tissue." ScienceDaily. ScienceDaily, 18 March 2011. <www.sciencedaily.com/releases/2011/03/110311153545.htm>.
DOE/Lawrence Berkeley National Laboratory. (2011, March 18). How breast cell communities organize into breast tissue. ScienceDaily. Retrieved March 31, 2015 from www.sciencedaily.com/releases/2011/03/110311153545.htm
DOE/Lawrence Berkeley National Laboratory. "How breast cell communities organize into breast tissue." ScienceDaily. www.sciencedaily.com/releases/2011/03/110311153545.htm (accessed March 31, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, March 31, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Solitair Device Aims to Takes Guesswork out of Sun Safety

Solitair Device Aims to Takes Guesswork out of Sun Safety

Reuters - Innovations Video Online (Mar. 31, 2015) — The Solitair device aims to take the confusion out of how much sunlight we should expose our skin to. Small enough to be worn as a tie or hair clip, it monitors the user&apos;s sun exposure by taking into account their skin pigment, location and schedule. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Soda, Salt and Sugar: The Next Generation of Taxes

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015) — Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline. Video provided by Washington Post
Powered by NewsLook.com
UnitedHealth Buys Catamaran

UnitedHealth Buys Catamaran

Reuters - Business Video Online (Mar. 30, 2015) — The $12.8 billion merger will combine the U.S.&apos; third and fourth largest pharmacy benefit managers. Analysts say smaller PBMs could also merge. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) — Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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