Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion

Sylvie Deborde, Laxmi Gusain, Ann Powers, Andrea Marcadis, Yasong Yu, Chun Hao Chen, Anna Frants, Elizabeth Kao, Laura H. Tang, Efsevia Vakiani, Masataka Amisaki, Vinod P. Balachandran, Annalisa Calo, Tatiana Omelchenko, Kristjan R. Jessen, Boris Reva, Richard J. Wong

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.

Original languageEnglish
Pages (from-to)2454-2473
Number of pages20
JournalCancer Discovery
Volume12
Issue number10
DOIs
StatePublished - 1 Oct 2022

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