March 1, 2012

Tumors begin when a cell goes rogue. These rogue cells turn against us in a most unforgiving way, even when their environment and neighboring cells try to put the kibosh on such behavior. Today’s image is from a fascinating paper describing how a single mutant cell in a highly organized environment can move out of the tissue, similar to what is seen in some tumors.

The development of a tumor begins with sporadic mutations of oncogenes, but these mutant cells are frequently in a highly organized tissue that limits its growth and movement, two key elements to the spread of cancer. A recent paper describes how single mutant cells are able to overcome their suppressive environment and move out of the tissue. To study this, Leung and Brugge grew mammalian cells in 3D cultures and followed clusters of cells with hollow lumens, called acini, after overexpressing different oncogenes. The overexpression of ERBB2, an oncogene overexpressed in 30% of breast tumors, caused outgrowth of the mutated cells from the cluster’s epithelial layer and into the lumen, a feature commonly seen in carcinoma in situ (non-invasive) breast tumors. In addition, Leung and Brugge found that this is a highly regulated process, as the mutation also causes changes in adhesion between the cell and its underlying matrix. These changes also support the survival and growth of the mutant cells. As seen in the images above, control cells (green, top) remained within the highly organized epithelial layer of the cluster over a course of 56 hours, but a single ERBB2-overexpressing cell (green, bottom) dissociated from the epithelial layer and moved into the hollow lumen.

Leung, C., & Brugge, J. (2012). Outgrowth of single oncogene-expressing cells from suppressive epithelial environments Nature, 482 (7385), 410-413 DOI: 10.1038/nature10826
Adapted by permission from Macmillan Publishers Ltd, copyright ©2012