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合成聚合物支架在乳腺癌三维组织培养和动物肿瘤模型中的应用。

Application of Synthetic Polymeric Scaffolds in Breast Cancer 3D Tissue Cultures and Animal Tumor Models.

作者信息

Rijal Girdhari, Bathula Chandra, Li Weimin

机构信息

Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99210, USA.

出版信息

Int J Biomater. 2017;2017:8074890. doi: 10.1155/2017/8074890. Epub 2017 Dec 17.

Abstract

Preparation of three-dimensional (3D) porous scaffolds from synthetic polymers is a challenge to most laboratories conducting biomedical research. Here, we present a handy and cost-effective method to fabricate polymeric hydrogel and porous scaffolds using poly(lactic-co-glycolic) acid (PLGA) or polycaprolactone (PCL). Breast cancer cells grown on 3D polymeric scaffolds exhibited distinct survival, morphology, and proliferation compared to those on 2D polymeric surfaces. Mammary epithelial cells cultured on PLGA- or PCL-coated slides expressed extracellular matrix (ECM) proteins and their receptors. Estrogen receptor- (ER-) positive T47D breast cancer cells are less sensitive to 4-hydroxytamoxifen (4-HT) treatment when cultured on the 3D porous scaffolds than in 2D cultures. Finally, cancer cell-laden polymeric scaffolds support consistent tumor formation in animals and biomarker expression as seen in human native tumors. Our data suggest that the porous synthetic polymer scaffolds satisfy the basic requirements for 3D tissue cultures both and . The scaffolding technology has appealing potentials to be applied in anticancer drug screening for a better control of the progression of human cancers.

摘要

对于大多数从事生物医学研究的实验室而言,用合成聚合物制备三维(3D)多孔支架是一项挑战。在此,我们展示了一种简便且经济高效的方法,可使用聚乳酸 - 乙醇酸共聚物(PLGA)或聚己内酯(PCL)制备聚合物水凝胶和多孔支架。与在二维聚合物表面生长的乳腺癌细胞相比,在3D聚合物支架上生长的乳腺癌细胞表现出不同的存活率、形态和增殖情况。在涂有PLGA或PCL的载玻片上培养的乳腺上皮细胞表达细胞外基质(ECM)蛋白及其受体。雌激素受体(ER)阳性的T47D乳腺癌细胞在3D多孔支架上培养时,对4 - 羟基他莫昔芬(4-HT)治疗的敏感性低于在二维培养条件下。最后,负载癌细胞的聚合物支架在动物体内支持形成与人类原发肿瘤中所见一致的肿瘤并表达生物标志物。我们的数据表明,多孔合成聚合物支架满足了体内和体外3D组织培养的基本要求。这种支架技术在抗癌药物筛选中具有诱人的应用潜力,有助于更好地控制人类癌症的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a841/5828246/070517019e50/IJBM2017-8074890.001.jpg

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