Nerve fibers in the tumor microenvironment in neurotropic cancer-pancreatic cancer and cholangiocarcinoma

Xiuxiang Tan, Shivan Sivakumar, Jan Bednarsch, Georg Wiltberger, Jakob Nikolas Kather, Jan Niehues, Judith de Vos-Geelen, Liselot Valkenburg-van Iersel, Svetlana Kintsler, Anjali Roeth, Guangshan Hao, Sven Lang, Marielle E. Coolsen, Marcel den Dulk, Merel R. Aberle, Jarne Koolen, Nadine T. Gaisa, Steven W. M. Olde Damink, Ulf P. Neumann, Lara R. Heij*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

27 Citations (Web of Science)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) are both deadly cancers and they share many biological features besides their close anatomical location. One of the main histological features is neurotropism, which results in frequent perineural invasion. The underlying mechanism of cancer cells favoring growth by and through the nerve fibers is not fully understood. In this review, we provide knowledge of these cancers with frequent perineural invasion. We discuss nerve fiber crosstalk with the main different components of the tumor microenvironment (TME), the immune cells, and the fibroblasts. Also, we discuss the crosstalk between the nerve fibers and the cancer. We highlight the shared signaling pathways of the mechanisms behind perineural invasion in PDAC and CCA. Hereby we have focussed on signaling neurotransmitters and neuropeptides which may be a target for future therapies. Furthermore, we have summarized retrospective results of the previous literature about nerve fibers in PDAC and CCA patients. We provide our point of view in the potential for nerve fibers to be used as powerful biomarker for prognosis, as a tool to stratify patients for therapy or as a target in a (combination) therapy. Taking the presence of nerves into account can potentially change the field of personalized care in these neurotropic cancers.

Original languageEnglish
Pages (from-to)899-908
Number of pages10
JournalOncogene
Volume40
Issue number5
Early online date7 Dec 2020
DOIs
Publication statusPublished - 4 Feb 2021

Keywords

  • MUSCARINIC ACETYLCHOLINE-RECEPTOR
  • PREDICTS POOR-PROGNOSIS
  • PERINEURAL INVASION
  • GROWTH-FACTOR
  • INTRAHEPATIC CHOLANGIOCARCINOMA
  • CLINICAL-SIGNIFICANCE
  • STELLATE CELLS
  • EXPRESSION
  • NEUROGENESIS
  • PROGRESSION

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