Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression
Year: 2024
Type: article
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.
Source: Life Science Alliance
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
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
Funders: U.S. Department of Defense, Teva Pharmaceutical Industries, Wake Forest University, METAvivor, Comprehensive Cancer Center at Wake Forest Baptist Medical Center, Jikei University School of Medicine, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: The contributions of sensory nerves to bone metastasis and associated bone pain, G1351188136, G2040153736, G2577419345, G4119534169, MOLECULAR CROSS-TALK: BONE METASTATIC PROSTATE CANCER AND NOCICEPTIVE NEURONS, A TARGETED ALPHA PARTICLE RADIOPHARMACEUTICAL FOR BONE METASTATIC BREAST CANCER, G7042415794, Defining and Targeting Lineage Transition Programs Operative in AR Pathway Independent Prostate Cancer, Cancer Center Support Grant, Targeting Vulnerabilities Exposed by Cancer Treatment-Induced Lineage Plasticity, The Pacific Northwest Prostate Cancer SPORE, Dissecting Neural Circuits Involved in Musculoskeletal Pain
OpenAlex ID: W4402472811