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Tension on gut muscles induces cell invasion in zebrafish intestine, mimicking cancer metastasis
Date:9/7/2012

PHILADELPHIA The stiffness of breast tissue is increasingly recognized as an important factor explaining the onset of breast cancer. Stiffening induces molecular changes that promote cancerous behavior in cells. Bioengineering studies have found that breast cancer cells grown on a 3-D gel have enhanced cell replication and decreased organization as rigidity increases. These signals are probably coordinated by surface proteins that communicate with connective tissue, to regulate cell replication, death, and movement. However, very little is known about how stiffness or other physical characteristics of tissues contributes to cancer behavior in living animals.

Towards a better understanding of how tissue stiffness drives cancer, in a new paper published in PLOS Biology this week, Michael Pack, MD, associate professor of Medicine, Perelman School of Medicine, University of Pennsylvania, and colleagues, show that epithelial cells lining the intestine of zebrafish that carry an activating mutation of the smooth muscle myosin gene form protrusions called invadopodia that allow the cells to invade surrounding connective tissue. The epithelial cell protrusions form in response to non-regulated contractions in the surrounding smooth muscle cells. These contractions generate oxidative stress in the epithelial cells, which has been linked to invadopodia formation in human cancer cells.

The zebrafish mutant is a novel living model to study how physical characteristics of a tissue can induce cells to invade surrounding tissues, the first step in cancer metastasis.

Epithelial cells of the digestive tract and many other organs are separated from their underlying connective tissue cells by a thin layer of extracellular matrix called the basement membrane. During cell invasion, epithelial cells breach the basement membrane and invade the adjacent connective tissue where the organ's blood vessels and lymphatic channels are located. Invasive ca
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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