| Literature DB >> 29191879 |
Camilla Engblom1,2, Christina Pfirschke1, Rapolas Zilionis3,4, Janaina Da Silva Martins5, Stijn A Bos6, Gabriel Courties1, Steffen Rickelt7, Nicolas Severe8, Ninib Baryawno8, Julien Faget9, Virginia Savova3, David Zemmour2,10, Jaclyn Kline1, Marie Siwicki1,2, Christopher Garris1,2, Ferdinando Pucci1, Hsin-Wei Liao1, Yi-Jang Lin1, Andita Newton1, Omar K Yaghi1,2, Yoshiko Iwamoto1, Benoit Tricot1, Gregory R Wojtkiewicz1, Matthias Nahrendorf1, Virna Cortez-Retamozo1, Etienne Meylan9, Richard O Hynes7, Marie Demay5, Allon Klein3, Miriam A Bredella6, David T Scadden8, Ralph Weissleder1,3,6, Mikael J Pittet11,6.
Abstract
Bone marrow-derived myeloid cells can accumulate within <span class="Disease">tumors and foster <span class="Disease">cancer outgrowth. Local immune-neoplastic interactions have been intensively investigated, but the contribution of the systemic host environment to tumor growth remains poorly understood. Here, we show in mice and cancer patients (n = 70) that lung adenocarcinomas increase bone stromal activity in the absence of bone metastasis. Animal studies reveal that the cancer-induced bone phenotype involves bone-resident osteocalcin-expressing (Ocn+) osteoblastic cells. These cells promote cancer by remotely supplying a distinct subset of tumor-infiltrating SiglecFhigh neutrophils, which exhibit cancer-promoting properties. Experimentally reducing Ocn+ cell numbers suppresses the neutrophil response and lung tumor outgrowth. These observations posit osteoblasts as remote regulators of lung cancer and identify SiglecFhigh neutrophils as myeloid cell effectors of the osteoblast-driven protumoral response.Entities:
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Year: 2017 PMID： 29191879 PMCID： PMC6343476 DOI： 10.1126/science.aal5081
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728