The Tumor Suppressor Pannexin1 Modulates Intercellular Binding

A novel three-dimensional growth chamber was used to determine how the tumor-suppressive protein Pannexin 1 (Panx1) functions to maintain cellular aggregates and reduce the likelihood of cancer progression.

Investigators at Brown University (Providence, RI, USA) worked with cultures of rat C6 glioma cells. These cells normally lack functioning Panx1. However, for this study, some C6 cells were genetically engineered to express Panx1.

The cells were cultured in novel three-dimensional growth chambers that provided them with a microenvironment that closely mimicked that found in vivo. Results published in the January 20, 2012, online edition of the Journal of Biological Chemistry revealed that after 24 hours in the growth chambers, cells with active Panx1 were able to form large multicellular tissues much faster and more tightly than the unaltered cancer cells.

Treatment with the drugs carbenoxolone (CBX) and probenecid (PBN), which directly and specifically block Panx1 channels respectively, confirmed that Panx1 was involved in accelerating aggregate assembly, and that exogenous ATP could reverse the inhibitive effects of CBX. These results indicated that Panx1 channels acted as conduits for ATP secretion that stimulated molecular pathways in the cell membrane linked to formation of stable intercellular bonds.

“In healthy tissues, the recently discovered protein Pannexin1 may be playing an important role in upholding the mechanical integrity of the tissue,” said first Brian Bao, doctoral student at Brown University. “When we develop cancer, we lose Pannexin1 and we lose this integrity. Using their single-cell systems, others have been able to carefully study individual pieces of this cascade. We came from a different perspective. Because the strength of our assay is that we can look at gross multicellular behavior in 3-D, we could ask, ‘Does this actually manifest into something tangible on the multicellular level?’

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