TY - JOUR
T1 - Nerve fibers in the tumor microenvironment in neurotropic cancer-pancreatic cancer and cholangiocarcinoma
AU - Tan, Xiuxiang
AU - Sivakumar, Shivan
AU - Bednarsch, Jan
AU - Wiltberger, Georg
AU - Kather, Jakob Nikolas
AU - Niehues, Jan
AU - de Vos-Geelen, Judith
AU - Valkenburg-van Iersel, Liselot
AU - Kintsler, Svetlana
AU - Roeth, Anjali
AU - Hao, Guangshan
AU - Lang, Sven
AU - Coolsen, Marielle E.
AU - den Dulk, Marcel
AU - Aberle, Merel R.
AU - Koolen, Jarne
AU - Gaisa, Nadine T.
AU - Olde Damink, Steven W. M.
AU - Neumann, Ulf P.
AU - Heij, Lara R.
PY - 2021/2/4
Y1 - 2021/2/4
N2 - 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.
AB - 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.
KW - MUSCARINIC ACETYLCHOLINE-RECEPTOR
KW - PREDICTS POOR-PROGNOSIS
KW - PERINEURAL INVASION
KW - GROWTH-FACTOR
KW - INTRAHEPATIC CHOLANGIOCARCINOMA
KW - CLINICAL-SIGNIFICANCE
KW - STELLATE CELLS
KW - EXPRESSION
KW - NEUROGENESIS
KW - PROGRESSION
U2 - 10.1038/s41388-020-01578-4
DO - 10.1038/s41388-020-01578-4
M3 - (Systematic) Review article
C2 - 33288884
SN - 0950-9232
VL - 40
SP - 899
EP - 908
JO - Oncogene
JF - Oncogene
IS - 5
ER -