Osteoblasts remotely supply lung tumors with cancer-promoting SiglecF(high) neutrophils.
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecF(high) neutrophils.
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DOI：
10.1126/science.aal5081
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发表时间：
2017-12-01
期刊：
影响因子：
--
通讯作者：
Pittet MJ
中科院分区：
文献类型：
--
作者：
Engblom C;Pfirschke C;Zilionis R;Da Silva Martins J;Bos SA;Courties G;Rickelt S;Severe N;Baryawno N;Faget J;Savova V;Zemmour D;Kline J;Siwicki M;Garris C;Pucci F;Liao HW;Lin YJ;Newton A;Yaghi OK;Iwamoto Y;Tricot B;Wojtkiewicz GR;Nahrendorf M;Cortez-Retamozo V;Meylan E;Hynes RO;Demay M;Klein A;Bredella MA;Scadden DT;Weissleder R;Pittet MJ
骨髓来源的髓系细胞可以在实体瘤中大量积聚，并调节促进癌症生长的功能。免疫与肿瘤在局部肿瘤微环境中的相互作用已经被深入研究，但宿主系统环境对肿瘤生长的贡献仍然知之甚少。在这里，我们在小鼠和癌症患者(n=70)中显示，即使在没有局部转移的情况下，肺腺癌也会增加骨基质的活性。动物研究进一步表明，癌症诱导的骨表型涉及骨驻留的骨钙素表达(OCN+)成骨细胞。这些细胞通过远程供应肿瘤浸润性SiglecFHigh中性粒细胞的不同亚群来促进癌症，这些中性粒细胞表现出离散的促癌特性。实验诱导的OCN+细胞数量的减少抑制了中性粒细胞的反应和肺癌的生长。这些观察揭示了成骨细胞作为肺癌远程调节者的作用，并确定SiglecFHigh中性粒细胞是成骨细胞驱动的亲肿瘤反应的髓系细胞效应器。
Bone marrow-derived myeloid cells can accumulate in high numbers within solid tumors and mediate functions that foster cancer outgrowth. Immune-neoplastic interactions in the local tumor microenvironment have been intensively investigated, but the contribution of the host systemic environment to tumor growth remains poorly understood. Here, we show in mice and in cancer patients (n= 70) that lung adenocarcinomas increase bone stromal activity even in the absence of local metastasis. Animal studies further 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 discrete cancer-promoting properties. Experimentally-induced reduction in the number of Ocn+ cells suppresses both the neutrophil response and lung tumor outgrowth. These observations uncover a role for osteoblasts as remote regulators of lung cancer and identify SiglecFhigh neutrophils as myeloid cell effectors of the osteoblast-driven pro-tumoral response.
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DOI：
10.1083/jcb.201002111
发表时间：
2010-09-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bozec A;Bakiri L;Jimenez M;Schinke T;Amling M;Wagner EF
通讯作者：
Wagner EF
影响因子：
10.1
作者：
Gabrilovich DI
通讯作者：
Gabrilovich DI
短链脂肪酸受体GPR43在人单核细胞中受XBP1调节。
影响因子：
4.6
作者：
Ang Z;Er JZ;Ding JL
通讯作者：
Ding JL
影响因子：
64.5
作者：
Cubillos-Ruiz JR;Silberman PC;Rutkowski MR;Chopra S;Perales-Puchalt A;Song M;Zhang S;Bettigole SE;Gupta D;Holcomb K;Ellenson LH;Caputo T;Lee AH;Conejo-Garcia JR;Glimcher LH
通讯作者：
Glimcher LH
影响因子：
48
作者：
Buch, T;Heppner, FL;Waisman, A
通讯作者：
Waisman, A