Dying cells encourage neighbors to grow

Researchers from The Rockefeller University have uncovered specific mechanisms by which cells that are genetically programmed to commit suicide stimulate growth in surrounding cells. The research, published online in Developmental Cell, provides new information about how normal, healthy tissues are maintained and may shed some light on a pathway that may contribute to tumor growth.

It has been known for some time that cells that die as a result of injury-provoked programmed cell death, also known as apoptosis, may stimulate the growth of surrounding cells. "Such compensatory mechanisms may be essential to allow for the elimination of as many damaged or dangerous cells as needed without compromising organismal fitness. In spite of its importance, the underlying mechanisms are poorly understood," explains study leader Dr. Hermann Steller.

Dr. Steller and colleagues demonstrate that when cells from the imaginal disc in the fruit fly Drosophila are stimulated to undergo apoptosis but experimentally manipulated so that they do not actually die ("undead cells"), they stimulate the growth of neighboring tissue. The researchers demonstrate that the undead cells promote cell growth in the surrounding imaginal disc by activating specific signaling cascades that are known to be required for cell proliferation. Although artificial, the experimental creation of undead cells allows this phenomenon to be expanded and studied. The authors provide evidence that apoptotic cells that are allowed to complete the process of dying also secrete the growth-stimulating signals.

The researchers conclude that apoptotic cells actively induce compensatory proliferation by activating growth-associated signaling pathways and secreting molecules that promote growth in surrounding tissues. They also suggest that abnormal regulation of apoptosis, as has been shown to be the case in some cancers, may result in pathological activation of these pathways. "Based on the behavior of undead cells in Drosophila imaginal discs, one might expect mutations that block or delay apoptosis to cause secondary proliferation and hyperplasia. It remains to be tested if such a mechanism contributes to hyperplasia in mouse models and human malignancies," offers Dr. Steller.

Hyung Don Ryoo, Travis Gorenc, and Hermann Steller: "Apoptotic Cells Can Induce Compensatory Cell Proliferation through the JNK and the Wingless Signaling Pathways"

Publishing in Developmental Cell, Volume 7, Number 4, October 2004, pages 491–501.

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