Injectable three-dimensional tumor microenvironments to study mechanobiology in ovarian cancer.
Injectable three-dimensional tumor microenvironments to study mechanobiology in ovarian cancer.
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DOI：
10.1016/j.actbio.2022.04.039
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发表时间：
2022-07-01
影响因子：
9.7
通讯作者：
Mehta, Geeta
中科院分区：
文献类型：
--
作者：
Horst, Eric N.;Novak, Caymen M.;Burkhard, Kathleen;Snyder, Catherine S.;Verma, Rhea;Crochran, Darel E.;Geza, Izabella A.;Fermanich, Wesley;Mehta, Pooja;Schlautman, Denise C.;Tran, Linh A.;Brezenger, Michael E.;Mehta, Geeta
关键词：
上皮性卵巢癌是最具侵袭性的妇科恶性肿瘤之一。尽管出现了聚腺苷二磷酸核糖聚合酶（PARP）和检查点抑制剂，但患者生存率的改善仍然有限。由于临床转化的部分限制，卵巢癌的有益治疗策略仍然难以捉摸。尽管细胞外蛋白（包括胶原蛋白、蛋白聚糖和糖蛋白）水平升高与化疗耐药有关，但它们在药物开发和筛选过程中经常缺失。来自细胞外基质 (ECM) 的生物物理和生化信号决定细胞表型并影响肿瘤进展和治疗反应。然而，许多最先进的肿瘤模型无法模拟肿瘤微环境（TME）的复杂性并忽略了关键的信号传导成分。在本文中，两种由藻酸盐-胶原蛋白或琼脂糖-胶原蛋白组成的互穿网络 (IPN) 水凝胶支架平台已被表征为可用作上皮性卵巢癌 ECM 的 3D 体外模型。这些高度可调、注塑模具兼容且廉价的 IPN 复制了卵巢 TME 中存在的关键控制物理和化学信号。此外，还建立了一种有效且对细胞友好的活细胞回收方法来回收封装后的细胞。最后，通过增加 3D 体外 ECM 模型内的支架刚度证明了卵巢癌的功能性机械转导。凭借这些特性，琼脂糖胶原和藻酸盐胶原水凝胶为上皮癌的机械生物学研究提供了强大的 TME。
Epithelial ovarian cancers are among the most aggressive forms of gynecological malignancies. Despite the advent of poly adenosine diphosphate-ribose polymerase (PARP) and checkpoint inhibitors, improvement to patient survival has been modest. Limited in part by clinical translation, beneficial therapeutic strategies remain elusive in ovarian cancers. Although elevated levels of extracellular proteins, including collagens, proteoglycans, and glycoproteins, have been linked to chemoresistance, they are often missing from the processes of drug- development and screening. Biophysical and biochemical signaling from the extracellular matrix (ECM) determine cellular phenotype and affect both tumor progression and therapeutic response. However, many state-of-the-art tumor models fail to mimic the complexities of the tumor microenvironment (TME) and omit key signaling components. In this article, two interpenetrating network (IPN) hydrogel scaffold platforms, comprising of alginate-collagen or agarose-collagen, have been characterized for use as 3D in vitro models of epithelial ovarian cancer ECM. These highly tunable, injection mold compatible, and inexpensive IPNs replicate the critical governing physical and chemical signaling present within the ovarian TME. Additionally, an effective and cell-friendly live-cell retrieval method has been established to recover cells post-encapsulation. Lastly, functional mechanotransduction in ovarian cancers was demonstrated by increasing scaffold stiffness within the 3D in vitro ECM models. With these features, the agarose-collagen and alginate-collagen hydrogels provide a robust TME for the study of mechanobiology in epithelial cancers.
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影响因子：
3.9
作者：
Ahearne, M;Yang, Y;Liu, KK
通讯作者：
Liu, KK
DOI：
10.1016/j.jmbbm.2008.12.007
发表时间：
2009-10-01
影响因子：
3.9
作者：
Buckley, Conor T.;Thorpe, Stephen D.;Kelly, Daniel J.
通讯作者：
Kelly, Daniel J.
DOI：
10.1039/c5ib00040h
发表时间：
2015-10
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Acerbi I;Cassereau L;Dean I;Shi Q;Au A;Park C;Chen YY;Liphardt J;Hwang ES;Weaver VM
通讯作者：
Weaver VM
DOI：
10.3390/ma8020799
发表时间：
2015-02-16
期刊：
Materials (Basel, Switzerland)
影响因子：
--
作者：
Baniasadi M;Minary-Jolandan M
通讯作者：
Minary-Jolandan M
影响因子：
5.2
作者：
Alkmin, Samuel;Brodziski, Rebecca;Campagnola, Paul J.
通讯作者：
Campagnola, Paul J.