Sun H Park,Shunsuke Tsuzuki,Kelly F Contino,Jenna Ollodart,Matthew R Eber,Yang Yu,Laiton R Steele,Hiroyuki Inaba,Yuko Kamata,Takahiro Kimura,Ilsa Coleman,Peter S Nelson,Enriqueta Muñoz-Islas,Juan Miguel Jiménez-Andrade,Thomas J Martin,Kimberly D Mackenzie,Jennifer R Stratton,Fang-Chi Hsu,Christopher M Peters,Yusuke Shiozawa
{"title":"Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression.","authors":"Sun H Park,Shunsuke Tsuzuki,Kelly F Contino,Jenna Ollodart,Matthew R Eber,Yang Yu,Laiton R Steele,Hiroyuki Inaba,Yuko Kamata,Takahiro Kimura,Ilsa Coleman,Peter S Nelson,Enriqueta Muñoz-Islas,Juan Miguel Jiménez-Andrade,Thomas J Martin,Kimberly D Mackenzie,Jennifer R Stratton,Fang-Chi Hsu,Christopher M Peters,Yusuke Shiozawa","doi":"10.26508/lsa.202302041","DOIUrl":null,"url":null,"abstract":"Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. In this study, we revealed that the cancer/sensory nerve crosstalk plays a crucial role in bone metastatic progression. We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory neuron-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo. This suggests that CGRP-expressing sensory nerves are involved in bone metastatic progression and that the CGRP/CRLR axis may serve as a potential therapeutic target for bone metastasis.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"197 1","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life Science Alliance","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.26508/lsa.202302041","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. In this study, we revealed that the cancer/sensory nerve crosstalk plays a crucial role in bone metastatic progression. We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory neuron-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo. This suggests that CGRP-expressing sensory nerves are involved in bone metastatic progression and that the CGRP/CRLR axis may serve as a potential therapeutic target for bone metastasis.
期刊介绍:
Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.