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Homeless cells find temporary lodging -- and their demise
Date:11/29/2007

for decades, nobody knew how they formed, says Brugge.

Overholtzer conducted additional experiments with his non-cancerous cell line. In collaboration with Guillaume Normand of Associate Professor of Cell Biology Randall Kings lab, he tracked the cells over time and was shocked to see that some of them actively bored into their neighbors. Furthermore, the invaders appeared to be healthy.

The fate of the internalized cells was even more surprising. While most of them eventually died, some exited their hosts and swam off unharmed. Still others divided inside their vacuoles, producing daughter cellsand additional proof of the invaders viability. Overholtzer stained the suspended cells for a protein associated with apoptosis to confirm that it was not playing a role.

Pathologists have speculated for years that some internalized cells are alive and our data suggests they were right, says Overholtzer.

Next, he looked at other human cell lines. A variety of them displayed entosis when tested, including four of nine tumor lines. Cancerous MCF7 cells proved particularly prone to invasions with a whopping 30 percent of them housing neighbors. These hospitable hosts invited additional experiments.

After 24 hours, 12 percent of MCF7 cells displayed massive cellular and nuclear degradation lacking apoptotic hallmarks. All of these cells were nestled inside vacuoles, and stains implicated acidification in their death.

He still doesnt know which cell orders the killing, but it appears the houseguest forces its way into the host. The initial contacts between MCF7 cells resemble the junctions established during a normal epithelial process that occurs when cells press against each other to form dense sheets. In suspension, epithelial cells may hijack this process to push into neighboring cells or to pull the membrane of a neighboring cell around them.

The simplest explanation is that entosis is an aberration of normal e
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Contact: Alyssa Kneller
public_affairs@hms.harvard.edu
617-432-0442
Harvard Medical School
Source:Eurekalert

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