N-cadherin in osteolineage cells modulates stromal support of tumor growth.
N-cadherin in osteolineage cells modulates stromal support of tumor growth.
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骨系细胞中的N-钙粘蛋白调节肿瘤生长的基质支持。
DOI：
10.1016/j.jbo.2021.100356
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发表时间：
2021-06
影响因子：
3.4
通讯作者：
Civitelli R
中科院分区：
文献类型：
--
作者：
Fontana F;Xiang J;Su X;Tycksen E;Nassau R;Fox G;Leanza G;Weilbaecher K;Civitelli R
N-钙粘素在骨线、Osterix+细胞中抑制骨外肿瘤的生长。Osterix+细胞存在于骨外肿瘤的间质微环境中。Osterix+T细胞存在于正常组织中，是转移频繁的部位。N-钙粘附素在肿瘤相关的Osterix+细胞中调节促肿瘤信号。肿瘤的生长和转移依赖于癌细胞和局部环境之间的相互作用。细胞-细胞黏附分子N-钙粘附素(Ncad)的表达与高侵袭性癌症有关，成骨细胞的表达被认为是为播散性肿瘤细胞在骨转移前的缝隙中建立的分子对接提供了分子对接。为了验证这一生物学模型，我们使用OSX-cre(CKO)有条件地删除了骨化细胞中的Ncad基因(CDH2)。与预期相反，转移性乳腺癌细胞系PYMT-BO1能够在骨中形成肿瘤，并在CKO和对照组小鼠中诱导骨溶解。尽管没有Ncad，从CKO小鼠分离的骨髓基质细胞能够与表达N-或E-钙粘素的肿瘤细胞进行直接的细胞-细胞相互作用。然而，与对照组相比，CKO组的皮下PYMT-BO1和B16F10肿瘤生长得更大。使用Ai9记者进行的细胞跟踪实验显示，在骨外肿瘤的间质和一小部分肺细胞中存在OSX+和Ncad+细胞。从骨外肿瘤分离的OSX+细胞的RNAseq基因表达分析显示，与对照OSX+细胞相比，CKO细胞中的促肿瘤信号通路发生了变化。因此，OSX+细胞中的Ncad不是建立骨转移所必需的，但在骨外肿瘤中，它通过微环境调节促肿瘤支持。
N-cadherin in osteolineage, Osterix+ cells restrains extraskeletal tumor growth. Osterix+ cells are present in the stromal microenvironment of extraskeletal tumors. Osterix+ cells are present in normal tissues frequent sites of metastasis. N-cadherin modulates pro-tumorigenic signaling in tumor associated Osterix+ cells. Tumor growth and metastases are dependent on interactions between cancer cells and the local environment. Expression of the cell–cell adhesion molecule N-cadherin (Ncad) is associated with highly aggressive cancers, and its expression by osteogenic cells has been proposed to provide a molecular “dock” for disseminated tumor cells to establish in pre-metastatic niches within the bone. To test this biologic model, we conditionally deleted the Ncad gene (Cdh2) in osteolineage cells using Osx-cre (cKO). Contrary to expectations, the metastatic breast cancer cell line PyMT-BO1 was able to form tumors in bone and to induce osteolysis in cKO as well as in control mice. Despite absence of Ncad, bone marrow stromal cells isolated from cKO mice were able to engage in direct cell–cell interactions with tumor cells expressing either N- or E-cadherin. However, subcutaneous PyMT-BO1 and B16F10 tumors grew larger in cKO relative to control littermates. Cell tracking experiments using the Ai9 reporter revealed the presence of Osx+ and Ncad+ cells in the stroma of extra-skeletal tumors and in a small population of lung cells. Gene expression analysis by RNAseq of Osx+ cells isolated from extra-skeletal tumors revealed alterations of pro-tumorigenic signaling pathways in cKO cells relative to control Osx+ cells. Thus, Ncad in Osx+ cells is not necessary for the establishment of bone metastases, but in extra-skeletal tumors it regulates pro-tumorigenic support by the microenvironment.
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影响因子：
4.6
作者：
Elisha Y;Kalchenko V;Kuznetsov Y;Geiger B
通讯作者：
Geiger B
影响因子：
20.3
作者：
Bromberg, Olga;Frisch, Benjamin J.;Calvi, Laura M.
通讯作者：
Calvi, Laura M.
DOI：
10.1126/science.aal5081
发表时间：
2017-12-01
期刊：
Science (New York, N.Y.)
影响因子：
--
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
通讯作者：
Pittet MJ
影响因子：
5.3
作者：
Hay, Eric;Laplantine, Emmanuel;Marie, Pierre J.
通讯作者：
Marie, Pierre J.
影响因子：
6.2
作者：
Lai, Chung Fang;Cheng, Su-Li;Civitelli, Roberto
通讯作者：
Civitelli, Roberto