Cruz-Neves Susana, Ribeiro Nilza, Graça Inês, Jerónimo Carmen, Sousa Susana R, Monteiro Fernando J
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
INEB-Instituto de Engenharia Biomédica, Divisão de Biomateriais, Universidade do Porto, Rua Alfredo Allen, Porto, 4200-135, Portugal.
J Biomed Mater Res A. 2017 Jul;105(7):2035-2046. doi: 10.1002/jbm.a.36070. Epub 2017 May 10.
Prostate cancer (PCa) is the second leading cause of death among men in Europe and U.S. The metastatic dissemination pattern of PCa is unique, developing bone metastasis as the only site of progression, consequently with a prognosis very poor. The cancer cells interactions within the surrounding bone environment are critical for tumor growth and progression. Secreted protein, acidic and rich in cysteine (SPARC) is described to be involved in PCa cells migration and invasion into bone. Three-dimensional (3D) in vitro systems that are able to closely resemble the in vivo microenvironment are recently taking importance in cancer research. Original nanohydroxyapatite/collagen scaffolds were designed to resemble bone microenvironment in order to be applied as substitutes in bone defects and as potential biomaterials to mimic skeletal tumors. In fact, these 3D structures were cytocompatible and able to support osteoblast (MC3T3-E1) colonization and to promote bone ingrowth. Additionally, SPARC adsorption onto the scaffolds affected PC3 and LNCaP PCa cell lines behavior. PC3 cells were found to adapt and colonize the scaffolds, differing from LNCaP where cells underwent morphogenic changes and grew as clusters. Furthermore, for the tested SPARC concentration, SPARC plays a role in retaining LNCaP cells at the latter time points while with PC3 cells no significant differences were observed. This characterization study is required to establish a bone model to provide new insights into the poorly understood PCa mechanisms of metastasis to bone and the generation of improved therapies. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2035-2046, 2017.
前列腺癌（PCa）是欧洲和美国男性中第二大主要死因。PCa的转移扩散模式独特，仅发展为骨转移这一进展部位，因此预后很差。癌细胞与周围骨环境的相互作用对肿瘤的生长和进展至关重要。分泌性蛋白质，富含半胱氨酸且呈酸性（SPARC）被描述为参与PCa细胞向骨的迁移和侵袭。能够紧密模拟体内微环境的三维（3D）体外系统最近在癌症研究中变得重要起来。最初设计的纳米羟基磷灰石/胶原蛋白支架旨在模拟骨微环境，以便用作骨缺损的替代物以及模拟骨骼肿瘤的潜在生物材料。事实上，这些3D结构具有细胞相容性，能够支持成骨细胞（MC3T3-E1）定植并促进骨向内生长。此外，支架上SPARC的吸附影响了PC3和LNCaP前列腺癌细胞系的行为。发现PC3细胞能够适应并在支架上定植，这与LNCaP细胞不同，后者会发生形态变化并聚集成簇生长。此外，对于测试的SPARC浓度，SPARC在后期时间点对保留LNCaP细胞起作用，而对于PC3细胞则未观察到显著差异。需要进行这项特性研究来建立一个骨模型，以便为人们了解甚少的PCa骨转移机制和开发改进疗法提供新的见解。© 2016威利期刊公司。《生物医学材料研究杂志》A部分：105A：2035 - 2046，2017年。
