Characterization and In Vivo Validation of a Three-Dimensional Multi-Cellular Culture Model to Study Heterotypic Interactions in Colorectal Cancer Cell Growth, Invasion and Metastasis.
Characterization and In Vivo Validation of a Three-Dimensional Multi-Cellular Culture Model to Study Heterotypic Interactions in Colorectal Cancer Cell Growth, Invasion and Metastasis.
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DOI：
10.3389/fbioe.2018.00097
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发表时间：
2018
影响因子：
5.7
通讯作者：
Rüegg C
中科院分区：
文献类型：
--
作者：
Cattin S;Ramont L;Rüegg C
在工业化国家，结直肠癌(CRC)是癌症相关死亡的第三大原因。局部侵袭和转移形成是与预后不良相关的事件，目前还没有有效的治疗选择。肿瘤的侵袭和转移受到肿瘤微环境细胞，特别是成纤维细胞和血管内皮细胞的强烈调控。解开肿瘤细胞和TME细胞之间的相互作用可能确定预防或治疗转移的新机制和治疗靶点。我们报道了一个三维肿瘤球体模型的建立和体内验证，以研究结直肠癌细胞、成纤维细胞和血管内皮细胞之间的相互作用。共培养的成纤维细胞可促进SW620和HCT116结直肠癌球体的侵袭，而SRC和FGFR激酶抑制剂Dasatinib和Erdafitinib分别可阻止这种作用。为了在体内验证这些发现，我们将SW620细胞单独或与成纤维细胞一起原位注射到小鼠盲肠内。与成纤维细胞联合注射可促进肺转移生长，而达沙替尼或厄达菲替尼治疗可完全逆转这一趋势。SW620或HCT116结直肠癌球体与内皮细胞共培养可抑制球体生长，但对癌细胞的迁移或侵袭无影响。与此体外效应一致，共注射内皮细胞在体内显著抑制了原发肿瘤的生长。从这些实验中，我们得出结论，在体外三维球体模型中，共培养的TME细胞和药物治疗对癌细胞侵袭和生长的影响，是体内效应的预测。三维球体模型可以作为研究异型细胞相互作用和药物活性对癌细胞影响的一个有吸引力的模型，作为动物实验的替代方案。这个模型可能会被修改和进一步发展，以包括不同类型的癌症和宿主细胞，并研究其他功能和药物。
Colorectal cancer (CRC) is the third cause of cancer-related mortality in industrialized countries. Local invasion and metastasis formation are events associated with poor prognosis for which today there are no effective therapeutic options. Invasion and metastasis are strongly modulated by cells of the tumor microenvironment (TME), in particular fibroblasts and endothelial cells. Unraveling interactions between tumor cells and cells of the TME may identify novel mechanisms and therapeutic targets to prevent or treat metastasis. We report here the development and in vivo validation of a 3D tumor spheroid model to study the interactions between CRC cells, fibroblasts and endothelial cells in vitro. Co-cultured fibroblasts promoted SW620 and HCT116 CRC spheroid invasion, and this was prevented by the SRC and FGFR kinase inhibitors Dasatinib and Erdafitinib, respectively. To validate these findings in vivo, we injected SW620 cells alone or together with fibroblasts orthotopically in the caecum of mice. Co-injection with fibroblasts promoted lung metastasis growth, which was fully reversed by treatment with Dasatinib or Erdafitinib. Co-culture of SW620 or HCT116 CRC spheroids with endothelial cells suppressed spheroid growth while it had no effect on cancer cell migration or invasion. Consistent with this in vitro effect, co-injected endothelial cells significantly inhibited primary tumor growth in vivo. From these experiments we conclude that effects on cancer cell invasion and growth induced by co-cultured TME cells and drug treatment in the 3D spheroid model in vitro, are predictive of in vivo effects. The 3D spheroid model may be considered as an attractive model to study the effect of heterotypic cellular interactions and drug activities on cancer cells, as animal testing alternative. This model may be adapted and further developed to include different types of cancer and host cells and to investigate additional functions and drugs.
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影响因子：
6.3
作者：
Golovko D;Kedrin D;Yilmaz ÖH;Roper J
通讯作者：
Roper J
DOI：
10.1016/j.mattod.2015.05.002
发表时间：
2015-12
期刊：
Materials today (Kidlington, England)
影响因子：
--
作者：
Asghar W;El Assal R;Shafiee H;Pitteri S;Paulmurugan R;Demirci U
通讯作者：
Demirci U
影响因子：
5.4
作者：
Dull, T;Zufferey, R;Naldini, L
通讯作者：
Naldini, L
3D生物打印：通过异质肿瘤微环境改善体外转移模型。
影响因子：
4.3
作者：
Albritton JL;Miller JS
通讯作者：
Miller JS
影响因子：
5.5
作者：
Bhome R;Bullock MD;Al Saihati HA;Goh RW;Primrose JN;Sayan AE;Mirnezami AH
通讯作者：
Mirnezami AH