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Getting organized: Berkeley Lab study shows how breast cell communities organize into breast tissue
Date:3/11/2011

e, 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 say
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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