Resolving cancer-stroma interfacial signalling and interventions with micropatterned tumour-stromal assays.
Resolving cancer-stroma interfacial signalling and interventions with micropatterned tumour-stromal assays.
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解决癌症菌的界面信号传导和微图案肿瘤 - 块状测定法的干预措施。
DOI：
10.1038/ncomms6662
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发表时间：
2014-12-09
影响因子：
16.6
通讯作者：
Parekkadan, Biju
中科院分区：
文献类型：
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作者：
Shen, Keyue;Luk, Samantha;Hicks, Daniel F.;Elman, Jessica S.;Bohr, Stefan;Iwamoto, Yoshiko;Murray, Ryan;Pena, Kristen;Wang, Fangjing;Seker, Erkin;Weissleder, Ralph;Yarmush, Martin L.;Toner, Mehmet;Sgroi, Dennis;Parekkadan, Biju
肿瘤-基质相互作用是癌症进展的决定性因素。在体内，相互作用界面与癌症和基质表型的空间分辨分布相关。在这里，我们建立了一个微图案化的肿瘤基质测定（μTSA）与激光捕获显微切割，以控制共培养细胞的位置，并分析散装和界面肿瘤基质信号在驱动癌症进展。μTSA揭示了与人雌激素受体阳性（ER+）乳腺癌样品一致的表型的空间分布，以及相对于肿瘤-基质界面的异质性药物活性。具体而言，一个未知的逆转机制显示在靶向肿瘤基质界面相互作用使用ER+ MCF-7乳腺癌和骨髓来源的基质细胞。逆转录酶通过减少肿瘤间质化（包括胶原沉积和活化的基质细胞的募集）来抑制体内MCF-7肿瘤生长和骨转移。本研究倡导μTSA作为研究肿瘤微环境相互作用和癌症场效应的平台，并应用于药物发现和开发。
Tumor-stromal interactions are a determining factor in cancer progression. In vivo, the interaction interface is associated with spatially-resolved distributions of cancer and stromal phenotypes. Here, we establish a micropatterned tumor-stromal assay (μTSA) with laser capture microdissection to control the location of co-cultured cells and analyze bulk and interfacial tumor-stromal signaling in driving cancer progression. μTSA reveals a spatial distribution of phenotypes in concordance with human estrogen receptor-positive (ER+) breast cancer samples, and heterogeneous drug activity relative to the tumor-stroma interface. Specifically, an unknown mechanism of reversine is shown in targeting tumor-stromal interfacial interactions using ER+ MCF-7 breast cancer and bone marrow-derived stromal cells. Reversine suppresses MCF-7 tumor growth and bone metastasis in vivo by reducing tumor stromalization including collagen deposition and recruitment of activated stromal cells. This study advocates μTSA as a platform for studying tumor microenvironmental interactions and cancer field effects with applications in drug discovery and development.
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影响因子：
--
作者：
Casbas-Hernandez P;Fleming JM;Troester MA
通讯作者：
Troester MA
影响因子：
5.7
作者：
D'Alise, Anna Morena;Amabile, Giovanni;Cortese, Riccardo
通讯作者：
Cortese, Riccardo
影响因子：
11.2
作者：
Gupta, Piyush B.;Proia, David;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
影响因子：
2.3
作者：
De Wever, Olivier;Pauwels, Patrick;De Craene, Bram;Sabbah, Michele;Emami, Shahin;Redeuilh, Gerard;Gespach, Christian;Bracke, Marc;Berx, Geert
通讯作者：
Berx, Geert
影响因子：
64.8
作者：
Garnett, Mathew J.;Edelman, Elena J.;Heidorn, Sonja J.;Greenman, Chris D.;Dastur, Anahita;Lau, King Wai;Greninger, Patricia;Thompson, I. Richard;Luo, Xi;Soares, Jorge;Liu, Qingsong;Iorio, Francesco;Surdez, Didier;Chen, Li;Milano, Randy J.;Bignell, Graham R.;Tam, Ah T.;Davies, Helen;Stevenson, Jesse A.;Barthorpe, Syd;Lutz, Stephen R.;Kogera, Fiona;Lawrence, Karl;McLaren-Douglas, Anne;Mitropoulos, Xeni;Mironenko, Tatiana;Thi, Helen;Richardson, Laura;Zhou, Wenjun;Jewitt, Frances;Zhang, Tinghu;O'Brien, Patrick;Boisvert, Jessica L.;Price, Stacey;Hur, Wooyoung;Yang, Wanjuan;Deng, Xianming;Butler, Adam;Choi, Hwan Geun;Chang, JaeWon;Baselga, Jose;Stamenkovic, Ivan;Engelman, Jeffrey A.;Sharma, Sreenath V.;Delattre, Olivier;Saez-Rodriguez, Julio;Gray, Nathanael S.;Settleman, Jeffrey;Futreal, P. Andrew;Haber, Daniel A.;Stratton, Michael R.;Ramaswamy, Sridhar;McDermott, Ultan;Benes, Cyril H.
通讯作者：
Benes, Cyril H.