Hsiao Amy Y, Torisawa Yu-suke, Tung Yi-Chung, Sud Sudha, Taichman Russell S, Pienta Kenneth J, Takayama Shuichi
Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA.
Biomaterials. 2009 Jun;30(16):3020-7. doi: 10.1016/j.biomaterials.2009.02.047. Epub 2009 Mar 21.
The niche microenvironment in which cancer cells reside plays a prominent role in the growth of cancer. It is therefore imperative to mimic the in vivo tumor niche in vitro to better understand cancer and enhance development of therapeutics. Here, we engineer a 3D metastatic prostate cancer model that includes the types of surrounding cells in the bone microenvironment that the metastatic prostate cancer cells reside in. Specifically, we used a two-layer microfluidic system to culture 3D multi-cell type spheroids of fluorescently labeled metastatic prostate cancer cells (PC-3 cell line), osteoblasts and endothelial cells. This method ensures uniform incorporation of all co-culture cell types into each spheroid and keeps the spheroids stationary for easy tracking of individual spheroids and the PC-3's residing inside them over the course of at least a week. This culture system greatly decreased the proliferation rate of PC-3 cells without reducing viability and may more faithfully recapitulate the in vivo growth behavior of malignant cancer cells within the bone metastatic prostate cancer microenvironment.
癌细胞所处的生态位微环境在癌症生长中起着重要作用。因此,在体外模拟体内肿瘤生态位对于更好地理解癌症和促进治疗方法的开发至关重要。在这里,我们构建了一个三维转移性前列腺癌模型,该模型包含转移性前列腺癌细胞所驻留的骨微环境中的周围细胞类型。具体而言,我们使用了两层微流控系统来培养荧光标记的转移性前列腺癌细胞(PC-3细胞系)、成骨细胞和内皮细胞的三维多细胞类型球体。这种方法确保了所有共培养细胞类型均匀地整合到每个球体中,并使球体保持静止,以便在至少一周的时间内轻松追踪各个球体以及其中驻留的PC-3细胞。这种培养系统在不降低活力的情况下大大降低了PC-3细胞的增殖率,并且可能更忠实地再现骨转移性前列腺癌微环境中恶性癌细胞的体内生长行为。