Calcitonin Related Polypeptide Alpha Mediates Oral Cancer Pain.

Autor: Tu NH; Department of Oral and Maxillofacial Surgery, Translational Research Center, New York University College of Dentistry, New York, NY 10010, USA., Inoue K; Department of Oral and Maxillofacial Surgery, Translational Research Center, New York University College of Dentistry, New York, NY 10010, USA., Lewis PK; Department of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, New York, NY 10010, USA., Khan A; Department of Oral and Maxillofacial Surgery, Translational Research Center, New York University College of Dentistry, New York, NY 10010, USA., Hwang JH; Department of Oral and Maxillofacial Surgery, Translational Research Center, New York University College of Dentistry, New York, NY 10010, USA., Chokshi V; Department of Oral and Maxillofacial Surgery, Translational Research Center, New York University College of Dentistry, New York, NY 10010, USA., Dabovic BB; Department of Pathology, NYU Langone Health, New York, NY 10010, USA., Selvaraj S; Department of Pathology, NYU Langone Health, New York, NY 10010, USA., Bhattacharya A; Department of Oral and Maxillofacial Surgery, Translational Research Center, New York University College of Dentistry, New York, NY 10010, USA., Dubeykovskaya Z; Department of Oral and Maxillofacial Surgery, Translational Research Center, New York University College of Dentistry, New York, NY 10010, USA., Pinkerton NM; Department of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, New York, NY 10010, USA., Bunnett NW; Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA.; Department of Neuroscience and Physiology, Neuroscience Institute, NYU Langone Health, New York, NY 10016, USA.; NYU Pain Research Center, New York University College of Dentistry, New York, NY 10010, USA., Loomis CA; Department of Pathology, NYU Langone Health, New York, NY 10010, USA., Albertson DG; Department of Oral and Maxillofacial Surgery, Translational Research Center, New York University College of Dentistry, New York, NY 10010, USA.; NYU Pain Research Center, New York University College of Dentistry, New York, NY 10010, USA., Schmidt BL; Department of Oral and Maxillofacial Surgery, Translational Research Center, New York University College of Dentistry, New York, NY 10010, USA.; Department of Neuroscience and Physiology, Neuroscience Institute, NYU Langone Health, New York, NY 10016, USA.; NYU Pain Research Center, New York University College of Dentistry, New York, NY 10010, USA.
Jazyk: angličtina
Zdroj: Cells [Cells] 2023 Jun 21; Vol. 12 (13). Date of Electronic Publication: 2023 Jun 21.
DOI: 10.3390/cells12131675
Abstrakt: Oral cancer patients suffer pain at the site of the cancer. Calcitonin gene related polypeptide (CGRP), a neuropeptide expressed by a subset of primary afferent neurons, promotes oral cancer growth. CGRP also mediates trigeminal pain (migraine) and neurogenic inflammation. The contribution of CGRP to oral cancer pain is investigated in the present study. The findings demonstrate that CGRP-immunoreactive (-ir) neurons and neurites innervate orthotopic oral cancer xenograft tumors in mice. Cancer increases anterograde transport of CGRP in axons innervating the tumor, supporting neurogenic secretion as the source of CGRP in the oral cancer microenvironment. CGRP antagonism reverses oral cancer nociception in preclinical oral cancer pain models. Single-cell RNA-sequencing is used to identify cell types in the cancer microenvironment expressing the CGRP receptor components, receptor activity modifying protein 1 Ramp1 and calcitonin receptor like receptor (CLR, encoded by Calcrl ). Ramp1 and Calcrl transcripts are detected in cells expressing marker genes for Schwann cells, endothelial cells, fibroblasts and immune cells. Ramp1 and Calcrl transcripts are more frequently detected in cells expressing fibroblast and immune cell markers. This work identifies CGRP as mediator of oral cancer pain and suggests the antagonism of CGRP to alleviate oral cancer pain.
Databáze: MEDLINE
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