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

Nerves are a component of the tumor microenvironment contributing to cancer progression, 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 t...

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Autores principales: Deborde, Sylvie, Gusain, Laxmi, Powers, Ann, Marcadis, Andrea, Yu, Yasong, Chen, Chun-Hao, Frants, Anna, Kao, Elizabeth, Tang, Laura H., Vakiani, Efsevia, Amisaki, Masataka, Balachandran, Vinod P., Calo, Annalisa, Omelchenko, Tatiana, Jessen, Kristjan R., Reva, Boris, Wong, Richard J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533012/
https://www.ncbi.nlm.nih.gov/pubmed/35881881
http://dx.doi.org/10.1158/2159-8290.CD-21-1690
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author Deborde, Sylvie
Gusain, Laxmi
Powers, Ann
Marcadis, Andrea
Yu, Yasong
Chen, Chun-Hao
Frants, Anna
Kao, Elizabeth
Tang, Laura H.
Vakiani, Efsevia
Amisaki, Masataka
Balachandran, Vinod P.
Calo, Annalisa
Omelchenko, Tatiana
Jessen, Kristjan R.
Reva, Boris
Wong, Richard J.
author_facet Deborde, Sylvie
Gusain, Laxmi
Powers, Ann
Marcadis, Andrea
Yu, Yasong
Chen, Chun-Hao
Frants, Anna
Kao, Elizabeth
Tang, Laura H.
Vakiani, Efsevia
Amisaki, Masataka
Balachandran, Vinod P.
Calo, Annalisa
Omelchenko, Tatiana
Jessen, Kristjan R.
Reva, Boris
Wong, Richard J.
author_sort Deborde, Sylvie
collection PubMed
description Nerves are a component of the tumor microenvironment contributing to cancer progression, 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. Nonmyelinating 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. This article is highlighted in the In This Issue feature, p. 2221
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spelling pubmed-95330122022-10-09 Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion Deborde, Sylvie Gusain, Laxmi Powers, Ann Marcadis, Andrea Yu, Yasong Chen, Chun-Hao Frants, Anna Kao, Elizabeth Tang, Laura H. Vakiani, Efsevia Amisaki, Masataka Balachandran, Vinod P. Calo, Annalisa Omelchenko, Tatiana Jessen, Kristjan R. Reva, Boris Wong, Richard J. Cancer Discov Research Articles Nerves are a component of the tumor microenvironment contributing to cancer progression, 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. Nonmyelinating 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. This article is highlighted in the In This Issue feature, p. 2221 American Association for Cancer Research 2022-10-05 2022-07-26 /pmc/articles/PMC9533012/ /pubmed/35881881 http://dx.doi.org/10.1158/2159-8290.CD-21-1690 Text en ©2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
spellingShingle Research Articles
Deborde, Sylvie
Gusain, Laxmi
Powers, Ann
Marcadis, Andrea
Yu, Yasong
Chen, Chun-Hao
Frants, Anna
Kao, Elizabeth
Tang, Laura H.
Vakiani, Efsevia
Amisaki, Masataka
Balachandran, Vinod P.
Calo, Annalisa
Omelchenko, Tatiana
Jessen, Kristjan R.
Reva, Boris
Wong, Richard J.
Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion
title Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion
title_full Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion
title_fullStr Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion
title_full_unstemmed Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion
title_short Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion
title_sort reprogrammed schwann cells organize into dynamic tracks that promote pancreatic cancer invasion
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533012/
https://www.ncbi.nlm.nih.gov/pubmed/35881881
http://dx.doi.org/10.1158/2159-8290.CD-21-1690
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