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Science. 2017 Dec 1;358(6367). pii: eaal5081. doi: 10.1126/science.aal5081.

Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils.

Author information

1
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA 02114, USA.
2
Graduate Program in Immunology, Harvard Medical School, Boston, MA 02115, USA.
3
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
4
Institute of Biotechnology, Vilnius University, Vilnius, LT 10257, Lithuania.
5
Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
6
Department of Radiology, Massachusetts General Hospital, MA 02114, USA.
7
Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
8
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
9
Swiss Institute for Experimental Cancer Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
10
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
11
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA 02114, USA. mpittet@mgh.harvard.edu.

Abstract

Bone marrow-derived myeloid cells can accumulate within tumors and foster 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.

PMID:
29191879
DOI:
10.1126/science.aal5081
[Indexed for MEDLINE]

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