Molecular Biology : Lawrence Berkeley National Lab - Breast cells undergoing rotation to form Acini

Research : by Nicholas Ellis @ http://www.youtube.com/sn1pe352

http://youtu.be/swehnPW20ko

http://youtu.be/oclQCb2W_sQ

http://youtu.be/6m3HLnd139M

http://youtu.be/MMhSaT6fS18

http://youtu.be/igyfSu3ACrE

http://youtu.be/qHf_o4hdBy8

http://youtu.be/Uz7zh-JCL2E

http://youtu.be/eVfSf1f95PY

http://youtu.be/WmztTKgfpGI

Berkeley Lab researchers have discovered a rotational motion in human breast cells that continues through mitosis and enables the cells and their progeny to form sphere-shaped acini.

"These observation suggested that acinus-forming nonmalignant mammary epithelial cells secrete factors that can suppress the phenotype of breast cancer cells growing in 3D cultures.

We hypothesized that such a complex phenotypical reversion is likely the result of multiple signaling factors that in combination allow cancer cells to form quiescent acinar-like structures.

We sought to identify and characterize these factors using solubility and size-fractionation of the conditioned medium from normal mammary epithelial cells, along with functional assays to identify the active molecules."

Fractionating the conditioned medium first by solubility revealed that its tumor suppressive activity could be divided into a morphogenic insoluble fraction and a cytotoxic soluble fraction.

Fractionating this cytotoxic soluble portion according to molecule size revealed that the most potent tumor cell--killing activity took place in the 10-to 50-kiloDalton range, which would be something the size of a protein.

Mass spectrometry was then used to identify the cytokine IL25 as the protein with the most potent cytotoxic activity.

Subsequent functional assays revealed that IL25 interacts with the IL25 receptor to activate apoptosis (cell death).

"We analyzed randomized cohorts of breast biopsy samples and found that 20-percent of the breast cancer samples tested were IL25 receptor-positive," Furuta says.

"Importantly, these IL25 receptor-positive tumors were highly invasive and correlated to poor clinical outcome patients.

We believe that in the future the IL25 receptor will serve as a novel therapeutic marker for breast cancer diagnosis and treatment."

Furuta says she and Bissell and their colleagues are now looking at five other proteins they discovered being secreted by normal developing breast cells.

While these other proteins are cytostatic rather than cytotoxic, meaning they stop the growth of cancer cells rather than kill the cells,

Furuta says she and her colleagues are investigating whether combinations of these other proteins with IL25 could prove to be an effective therapy against some forms of especially aggressive breast and other cancers.

This work was primarily supported by a grant from the National Institutes of Health's National Cancer Institute.

Contacts and sources:

Lynn Yarris

DOE/Lawrence Berkeley National Laboratory

Lawrence Berkeley National Laboratory addresses the world's most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe.

Founded in 1931, Berkeley Lab's scientific expertise has been recognized with 12 Nobel prizes.

The University of California manages Berkeley Lab for the U.S. Department of Energy's Office of Science. For more, visit www.lbl.gov.

For more information about the research of Mina Bissell, visit her Website at

http://www.lbl.gov/LBL-Programs/lifesciences/BissellLab/main.html

Category:

Science & Technology

Tags:

• Molecular
• Biology
• Breast
• cells
• undergoing
• rotation
• to
• form
• Acini

[sn1pe352]

Berkeley Lab researchers have discovered a rotational motion in human breast cells that continues through mitosis and enables the cells and their progeny to form sphere-shaped acini.

"These observation suggested that acinus-forming nonmalignant mammary epithelial cells secrete factors that can suppress the phenotype of breast cancer cells growing in 3D cultures.

[sn1pe352]

We hypothesized that such a complex phenotypical reversion is likely the result of multiple signaling factors that in combination allow cancer cells to form quiescent acinar-like structures.

We sought to identify and characterize these factors using solubility and size-fractionation of the conditioned medium from normal mammary epithelial cells, along with functional assays to identify the active molecules."