Dorsoventral Polarity Guides Confined Migration of Cancer Cells By Emily Wisniewski and Gina Wadas Metastasis is a complex process that requires cancer cells to adapt to diverse environments in the body. After they escape from the primary tumor, the cells embark on a long journey to colonize distant organs by migrating through a maze of three-dimensional tracks created by various anatomical structures. The tracks, or channels, form between adjacent extracellular matrix fibers (collagen), or between
Dorsoventral polarity orients cells to the geometry of their environment. Once cells sense the geometry around them, they respond by altering their signaling and mode of migration. Emily Wisniewski and Panagiotis Mistriotis, under the direction of Konstantinos Konstantopoulos, along with other colleagues, sought to understand the role that dorsoventral polarity plays in cancer cell migration.
“We demonstrated for the first time that physical confinement stiffens the cell nucleus, which has direct implications on the mechanisms of cell migration.” nerves, muscles and their connective tissue. Once the channels are established, the cancerous cells use them to move efficiently to different parts of the body like a highway system. During metastasis, important motor proteins and signaling molecules organize themselves asymmetrically along the front-to-rear cell axis in a phenomenon called cell polarity. This polarity establishes directionality and is essential for persistent cell migration. Although the importance of front-to-rear cell polarity is well understood, it is not known whether metastasizing cancer cells also exhibit dorsoventral polarity, or polarity along their top-tobottom cell axis. 14 research
“Previous work has only examined top to bottom cellular asymmetry in non-cancerous, epithelial tissues,” Mistriotis said. “Our studies, performed both in vitro and in vivo, are the first to identify and characterize the important role of dorsoventral polarity during cancer cell migration.” Wisniewski is a PhD candidate in the Department of Chemical and Biomolecular Engineering at Johns Hopkins, and Mistriotis, is a former postdoctoral fellow at Johns Hopkins and currently an Assistant Professor at Auburn University. Konstantopoulos is a professor and core faculty member at the INBT and William H. Schwarz Professor of Chemical and Biomolecular Engineering.
