"We've discovered a novel type of cell motility where single cells undergo multiple rotations and cohesively maintain that rotational motion as they divide and assemble into acini," says Tanner. "We've also demonstrated that this CAMo is a critical function for the establishment of spherical architecture and not simply a consequence of multicellular aggregates. If CAMo is disrupted, the final geometry is not a sphere."
Working with both immortalized and primary human epithelial cells, cultured in a unique 3D gel that serves as a surrogate for the basement membrane (an assay developed by Bissell and colleagues two decades ago), and using 4D live-imaging (3D plus time) confocal microscopy, Tanner, Bissell and their colleagues found that CAMo arises from a centripetal force generated by the flexing of crescent-shaped muscle-like molecules called actomyosin in the cell's cytoskeleton. This centripetal force sets the cell to rotating about an axis. The rotation is slow, barely once an hour, it may run clockwise or counterclockwise, and its axis might shift, but this rotational motion is cohesive. It continues as the cell divides and the subsequent progeny form into acini, bestowing on cells and acini the polarity and the cavity needed for proper form and function.
"Without CAMo, the cells lose their way and do not form structures that allow mammary cells to make and secrete milk," says Tanner. "In order to form a polarized sphere, the cells have to be properly oriented so that certain components are up and certain components are down. The CAMo rotation provides the cells with this orientation."
Bissell is renowned for her pioneering work that elucidated the critical role in breast cancer development played by the extracellular matrix (ECM), a network of fibrous and globular proteins in the microenvironment that surrounds a breast cell. Her experiments have shown that w
|Contact: Lynn Yarris|
DOE/Lawrence Berkeley National Laboratory