Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression.

IF 3.3 2区 生物学 Q1 BIOLOGY
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
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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.
骨转移癌细胞与感觉神经在骨转移过程中的相互影响
尽管外周神经在癌症进展中的作用已得到重视,但人们对癌症/感觉神经串扰及其对骨转移和相关疼痛的作用却知之甚少。在这项研究中,我们发现癌症/感觉神经串扰在骨转移过程中起着至关重要的作用。我们发现:(i) 骨转移小鼠的骨膜感觉神经表达降钙素基因相关肽(CGRP);(ii) 骨转移癌症患者血清中 CGRP 水平升高;(iii) 骨转移患者肿瘤样本中降钙素受体样受体(CRLR,CGRP 受体的一种成分)表达升高;(iv) 癌症患者较高的 CRLR 水平与无复发生存期呈负相关;(v) CGRP 通过 CRLR/p38/HSP27 途径诱导癌细胞增殖;以及 (vi) 阻断感觉神经元产生的 CGRP 可减少体外癌细胞增殖和体内骨转移进展。这表明表达 CGRP 的感觉神经参与了骨转移的进展,CGRP/CRLR 轴可作为骨转移的潜在治疗靶点。
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来源期刊
Life Science Alliance
Life Science Alliance Agricultural and Biological Sciences-Plant Science
CiteScore
5.80
自引率
2.30%
发文量
241
审稿时长
10 weeks
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.
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