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Human breast cancer cells growing in the lab on a three-dimensional (3-D) extracellular matrix reverted to a normal phenotype when subjected to compression force applied by an elastic chamber, researchers reported on Dec. 17 at the American Society for Cell Biology Annual Meeting in San Francisco.
Gautham Venugopalan, PhD, of the University of California, Berkeley, bioengineering lab of Daniel Fletcher, PhD, described how applying compressive force to malignant breast epithelial cells growing within a laminin-rich 3-D extracellular matrix caused them to turn into highly organized, growth-arrested acini, the milk-secreting spherical structures that are central to breast tissue.
This "phenotypic reversion" was accomplished without pharmacological agents, noted Dr. Venugopalan. Research collaborators included Kandice Tanner, PhD, and Mina Bissell, PhD, of the Lawrence Berkeley National Laboratory in Berkeley.
During a woman's reproductive life, breast tissue continuously grows, shrinks, and remodels in a highly regulated fashion. When this process breaks down, growth becomes abnormal.
Although genetic mutations are the classic explanation for differences between healthy and malignant cells but they don't tell the whole story because malignant cells treated with certain drugs will grow into organized acini that appear very similar to the healthy acini, even though they remain genetically malignant. This indicates that malignant cells have not completely "forgotten" how to be healthy, since they can be guided back into their "normal" growth program by giving them the right cues, according to Dr. Venugopalan.
Could mechanical force also reprogram malignant cells? The researchers seeded malignant breast epithelial cells into a 3-D laminin-rich extracellular matrix and used an elastic chamber to apply a compressive force. Over time, the compressed malignant cells grew into more organized, healthy-looking acini that resembl
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