Reprogrammed Schwann cells organize into dynamic tracks that promote pancreatic cancer invasion Journal Article
| Authors: | Deborde, S.; Gusain, L.; Powers, A.; Marcadis, A.; Yu, Y.; Chen, C. H.; Frants, A.; Kao, E.; Tang, L. H.; Vakiani, E.; Amisaki, M.; Balachandran, V. P.; Calo, A.; Omelchenko, T.; Jessen, K. R.; Reva, B.; Wong, R. J. |
| Article Title: | Reprogrammed Schwann cells organize into dynamic tracks that promote pancreatic cancer invasion |
| Abstract: | Nerves are a component of the tumor microenvironment contributing to cancer pro-gression, but the role of cells from nerves in facilitating cancer invasion remains poorly understood. Here we show that Schwann cells (SC) activated by cancer cells collectively function as tumor-activated Schwann cell tracks (TAST) that promote cancer cell migration and invasion. Nonmyeli-nating SCs form TASTs and have cell gene expression signatures that correlate with diminished survival in patients with pancreatic ductal adenocarcinoma. In TASTs, dynamic SCs form tracks that serve as cancer pathways and apply forces on cancer cells to enhance cancer motility. These SCs are activated by c-Jun, analogous to their reprogramming during nerve repair. This study reveals a mechanism of cancer cell invasion that co-opts a wound repair process and exploits the ability of SCs to collectively organize into tracks. These findings establish a novel paradigm of how cancer cells spread and reveal therapeutic opportunities. SIGNIFICANCE: How the tumor microenvironment participates in pancreatic cancer progression is not fully understood. Here, we show that SCs are activated by cancer cells and collectively organize into tracks that dynamically enable cancer invasion in a c-Jun–dependent manner. See related commentary by Amit and Maitra, p. 2240. © 2022 The Authors; Published by the American Association for Cancer Research. |
| Keywords: | genetics; pancreatic neoplasms; metabolism; carcinoma, pancreatic ductal; cell motion; pathology; pancreas carcinoma; pancreas tumor; cell movement; schwann cell; tumor microenvironment; schwann cells; humans; human |
| Journal Title: | Cancer Discovery |
| Volume: | 12 |
| Issue: | 10 |
| ISSN: | 2159-8274 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2022-10-01 |
| Start Page: | 2454 |
| End Page: | 2473 |
| Language: | English |
| DOI: | 10.1158/2159-8290.Cd-21-1690 |
| PUBMED: | 35881881 |
| PROVIDER: | scopus |
| PMCID: | PMC9533012 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2022 -- Source: Scopus |
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