Pancreatic cancer is notorious for its affinity for invading nerves. A new study using a systematic unbiased RNA-interference screen of neuronal chemokines in cocultures of mouse sensory neurons and pancreatic cancer cells has now identified CCL21 and CXCL10 as key mediators of neural invasion, neural remodelling and pain in pancreatic cancer.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Transcriptional control of pancreatic cancer immunosuppression by metabolic enzyme CD73 in a tumor-autonomous and -autocrine manner
Nature Communications Open Access 08 June 2023
-
[99mTc]Tc-Galacto-RGD2 integrin αvβ3-targeted imaging as a surrogate for molecular phenotyping in lung cancer: real-world data
EJNMMI Research Open Access 13 June 2021
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Liebl, F. et al. The impact of neural invasion severity in gastrointestinal malignancies: a clinicopathological study. Ann. Surg. 260, 900–907 (2014).
Amit, M. et al. Upregulation of RET induces perineurial invasion of pancreatic adenocarcinoma. Oncogene 36, 3232–3239 (2017).
Gil, Z. et al. Paracrine regulation of pancreatic cancer cell invasion by peripheral nerves. J. Natl Cancer Inst. 102, 107–118 (2010).
Demir, I. E. et al. Investigation of Schwann cells at neoplastic cell sites before the onset of cancer invasion. J. Natl Cancer Inst. 106, dju184 (2014).
Deborde, S. et al. Schwann cells induce cancer cell dispersion and invasion. J. Clin. Invest. 126, 1538–54 (2016).
Demir, I. E. et al. Early pancreatic cancer lesions suppress pain through CXCL12-mediated chemoattraction of Schwann cells. Proc. Natl Acad. Sci. USA 114, E85–E94 (2017).
Na’ara, S., Amit, M. & Gil, Z. L1CAM induces perineural invasion of pancreas cancer cells by upregulation of metalloproteinase expression. Oncogene 38, 596–608 (2019).
Hirth, M. et al. CXCL10 and CCL21 promote migration of pancreatic cancer cells toward sensory neurons and neural remodeling in tumors in mice, associated with pain in patients. Gastroenterology https://doi.org/10.1053/j.gastro.2020.04.037 (2020).
Ceyhan, G. O. et al. Pancreatic neuropathy and neuropathic pain — a comprehensive pathomorphological study of 546 cases. Gastroenterology 136, 177–186 (2009).
Marchesi, F. et al. The chemokine receptor CX3CR1 is involved in the neural tropism and malignant behavior of pancreatic ductal adenocarcinoma. Cancer Res. 68, 9060–9069 (2008).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Demir, I.E., Mota Reyes, C. Chemokines: the (un)usual suspects in pancreatic cancer neural invasion. Nat Rev Gastroenterol Hepatol 18, 221–222 (2021). https://doi.org/10.1038/s41575-020-0329-1
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41575-020-0329-1
This article is cited by
-
Transcriptional control of pancreatic cancer immunosuppression by metabolic enzyme CD73 in a tumor-autonomous and -autocrine manner
Nature Communications (2023)
-
[99mTc]Tc-Galacto-RGD2 integrin αvβ3-targeted imaging as a surrogate for molecular phenotyping in lung cancer: real-world data
EJNMMI Research (2021)