The Boring Schwann Cells: Tumor Me-TAST-asis along Nerves

Abstract

Perineural spread is an ominous feature of cancer. Here, Deborde and colleagues describe for the first time the biophysical coupling driving this route of tumor spread and the role of Schwann cell activation in the mobilization of cancer cells within and along the tumor-associated nerves. See related article by Deborde et al., p. 2454 (8).

Figure 1.

Activated Schwann cells pave the way for cancer to disseminate along nerves. Deborde and colleagues analyzed pancreatic cancers using clinical data, 3D models, and mouse models. A, Schwann cell activation, TAST formation, and cancer cell mobilization along the nerve. Tumor cells induce a nerve injury transcriptional program in Schwann cells. This transcriptional program that leads to Schwann cell activation is c-Jun dependent. c-Jun governs major aspects of the nerve injury response, determines the level of expression of trophic factors and adhesion molecules, regulates the formation of regeneration tracks and myelin clearance, and controls the distinctive regenerative potential of peripheral nerves. Active Schwann cells acquire motor functions that include cytoplasmic actin reorganization and allow for their migration among nerve fascicles. These Schwann cells degrade the extracellular matrix to form intraneural tunnels (i.e., TASTs), organize the cancer cells in chains within these tunnels, and push and pull the cancer cells along the nerve. B, c-Jun regulates perineural invasion in vivo. When c-Jun–deficient mice received transplants of PDAC cells via direct injection into the sciatic nerve, no progression of cancer cells was noted and the hind limb function was preserved, unlike in c-Jun wild-type (WT) animals. KO, knockout.