Many a cancer study seeks to tally dangerous mutations, but factors besides genes may yield insights that are just as important. Two laboratories at the annual meeting of the American Society for Cell Biology in San Francisco this week presented work on cancer-relevant findings that are independent of particular mutations:?one group shows that a?few minutes? compression reverts malignant cells to normal, another that changes in breasts? cellular composition may remove barriers for malignant growth.
Malignant breast epithelial cells usually grow in disorganized masses (left), but if subjected to a few minutes of compression, they form normal-looking structures (right).
ASCB; Fletcher lab, UC Berkeley
Mark LaBarge from Lawrence Berkeley National laboratory and colleagues examined how healthy breast tissue varied as women age, and found marked changes in its composition. They sorted out cells in tissue that had been removed for reasons besides cancer, such as breast reduction or augmentation. Tissue from younger women consisted of about 2-3% of duct-lining cells called luminal cells and 70 to 90% myoepithelial cells, which help squeeze milk into ducts during lactation. In older women, the two cell types occurred in nearly equal proportions. What?s more, cellular composition and other changes correlated almost perfectly with subjects? ages.
Before these studies, most in-depth studies had looked at tissue from women in their teens and twenties, says LaBarge. ?When we looked at our older people we were shocked. We were pretty startled to find out that the epithelium completely changes its character.?
Myoepithelial cells are believed to function as tumour suppressors, and numbers of luminal cells are thought to correlate with those of multipotent progenitors, which gives rise to several cell types. These cells are also thought to contribute to most breast cancers.
LaBarge believes that this makes for a situation where mutations that occur in younger women may not lead to cancer until they grow older. ?Aging takes away enough gatekeepers,? until the cells with dangerous mutations start to behave abnormally.
Figuring out exactly how this happens will be a collaborative effort. A culture technique for growing cells from healthy tissue seems to preserve cell characteristics and proportions remarkably well. This will allow LaBarge to share materials and conduct more experiments. ?We can actually model the aged microenvironment one layer at a time.?
Not far from LaBarge?s laboratory, Gautham Venugopalan has been exploring how a short burst of pressure can prevent breast cancer cells from forming tumours. His group suspends cells in a gel to which a brief compression pulse is applied. Afterwards, instead of growing into tumours, the cells form organized, star-shaped structures, typical of normal cells. The results are suprising, says Venugopalan, who received his PhD earlier this month from Daniel Fletcher?s laboratory at the University of California, Berkeley.
The pressure does not change the cells genetically. ?If you sequenced them, you?d think that they would still be malignant,? he says. ?By applying pressure, we are encouraging these cells to communicate with each other in a more normal way.?
The cell-surface molecule E-cadherin seems to be involved: blocking it causes malignant cells to go on to form unstructured tumours whether or not they had been subjected to a compressive force. Microvideos showed that, to form the non-tumorous organized structures, breast epithelial cells stick together and rotate around each other. ?They do a little dance,? says Venugopalan. ?Malignant cells don?t dance together,?
Now Venugopalan?s lab is trying to figure out how bursts of pressure act within a cell to encourage such graceful behavior. The next steps in learning this dance could be the first steps toward a drug.
Source: http://blogs.nature.com/news/2012/12/breast-cancer-behaviour-more-than-mutations.html
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