Fang Josephine Y, Tan Shih-Jye, Wu Yi-Chen, Yang Zhi, Hoang Ba X, Han Bo
Nimni-Cordoba Tissue Engineering and Drug Discovery Laboratory, Division of Plastic and Reconstructive Surgery, Departments of Surgery and Biomedical Engineering, Keck School of Medicine, University of Southern California, 1333 San Pablo St., BMT 302, Los Angeles, CA, 90089, USA.
J Transl Med. 2016 Feb 4;14:38. doi: 10.1186/s12967-016-0798-8.
The heterogeneous and dynamic tumor microenvironment has significant impact on cancer cell proliferation, invasion, drug response, and is probably associated with entering dormancy and recurrence. However, these complex settings are hard to recapitulate in vitro.
In this study, we mimic different restriction forces that tumor cells are exposed to using a physiologically relevant 3D model with tunable mechanical stiffness.
Breast cancer MDA-MB-231, colon cancer HCT-116 and pancreatic cancer CFPAC cells embedded in the stiffer gels exhibit a changed morphology and cluster formation, prolonged doubling time, and a slower metabolism rate, recapitulating the pathway from competency to dormancy. Altering environmental restriction allows them to re-enter and exit dormant conditions and change their sensitivities to drugs such as paclitaxol and gemcitabine. Cells surviving drug treatments can still regain competent growth and form tumors in vivo.
We have successfully developed an in vitro 3D model to mimic the effects of matrix restriction on tumor cells and this high throughput model can be used to study tumor cellular functions and their drug responses in their different states. This all in one platform may aid effective drug development.
异质性和动态的肿瘤微环境对癌细胞的增殖、侵袭、药物反应有重大影响，并且可能与进入休眠状态和复发有关。然而，这些复杂的情况很难在体外重现。
在本研究中，我们使用具有可调机械刚度的生理相关三维模型模拟肿瘤细胞所面临的不同限制力。
嵌入较硬凝胶中的乳腺癌MDA-MB-231细胞、结肠癌HCT-116细胞和胰腺癌CFPAC细胞表现出形态改变和聚集体形成、倍增时间延长以及代谢率降低，重现了从增殖能力到休眠状态的过程。改变环境限制可使它们重新进入和退出休眠状态，并改变它们对紫杉醇和吉西他滨等药物的敏感性。经药物处理后存活的细胞仍可恢复增殖能力并在体内形成肿瘤。
我们成功开发了一种体外三维模型来模拟基质限制对肿瘤细胞的影响，这种高通量模型可用于研究肿瘤细胞在不同状态下的功能及其药物反应。这个一体化平台可能有助于有效的药物开发。
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