How sporadic mutant cells evolve within the tightly regulated environment of otherwise normal tissues has remained elusive.

A model to help understand how cancer develops from a single oncogene-expressing cell is presented in Nature this week. The results show that initial tumour cell outgrowth is a highly regulated process.

Three-dimensional (3D) cell cultures provide a means for examining single-cell evolution, which is not always easy to study within native tissues.

Cheuk Leung and Joan Brugge have induced oncogene expression in single cells in a 3D model of human-derived mammary epithelial cells to mimic the very first stages of tumorigenesis.

The authors elucidate the mechanisms involved in tumour cell outgrowth and identify pathways that regulate this process.

Furthermore, they show that translocation of cells out of the epithelial layer allows them to escape the suppressive influences of the epithelial environment. This event leads to outgrowths outside their native niches which resemble early in situ tumour lesions.
 

The findings raise the possibility that mechanisms such as cell translocation or compromising tissue integrity may initiate abnormal proliferation from dormant mutant cells.
 

Source: Nature

Article: 10.1038/nature10826