PO.MCB10.01 · 分子与细胞生物学
脂肪细胞条件培养基增强前列腺癌细胞系的增殖、运动和侵袭：microRNA的参与
Adipocyte-conditioned medium enhances the proliferation, motility and invasion of prostate cancer cell lines: Involvement of the microRNAs
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摘要 Abstract
中文摘要
脂肪细胞（如前列腺周围脂肪组织、骨髓）是前列腺癌肿瘤微环境中的关键组分之一。据报道，脂肪细胞通过脂肪细胞因子和外泌体影响前列腺癌细胞的行为。我们此前已展示了脂肪细胞条件培养基（CM）对DU145前列腺癌细胞行为的影响，并通过微阵列分析了在CM中培养的DU145细胞的microRNA谱。在本研究中，另外加入了两种细胞系（LNCaP和PC-3）以分析细胞行为。CM增强了PC-3细胞的增殖、运动和侵袭，与DU-145相同，而未增强LNCaP的这些行为，提示CM促进雄激素非依赖性癌细胞行为。然而，在CM条件下的侵袭实验中，DU145和PC-3细胞表现出不同的阿米巴样-间充质转化可塑性，提示CM的效应涉及依赖于细胞系的不同机制。此外，我们重新分析了DU145和PC-3细胞的microRNA谱，使用miRDB和Target Scan验证了靶标评分，使用GEPIA和Human Protein Atlas评估总生存和无病生存，以识别候选靶基因。我们还使用DepMap确认了这些候选靶基因在DU145和PC3细胞中的表达水平。这些结果提示，CM可能通过microRNA-5787及其多个靶基因（如WWOX和FLNA）影响前列腺癌细胞的行为。
查看英文原文 English abstract
Adipocytes (e.g., periprostatic adipose tissues, bone marrow) are one of the critical components in the prostate cancer tumor microenvironment. It has been reported that adipocytes influence the behavior of prostate cancer cells through adipocytokines and exosomes. We have previously shown effects of conditioned medium (CM) from adipocytes in behaviors of DU145 prostate cancer cells, and analyzed the microRNA profile of DU145 cells cultured in CM by a microarray. In this study, two additional cell lines (LNCaP and PC-3)were added to analyze cell behaviors. CM enhanced the proliferation, motility and invasion of PC-3 cells as same as DU-145 while not enhanced these behaviors of LNCaP, suggesting that CM promote androgen-independent cancer cell behaviors. However, in the invasion assay under CM, DU145 and PC-3 cells showed different amoeboid-mesenchymal transition plasticity, suggesting that effects of CM involve different mechanisms depending on the cell line. In addition, we re-analyzed the microRNA profiles of DU145 and PC-3 cells, verified target scores using miRDB and Target Scan, assessed overall survival and disease-free survival using GEPIA and Human Protein Atlas to identify candidate target genes. We also confirmed the expression levels of these candidate target genes in DU145 and PC3 cells using the DepMap. These results suggest that CM may affect behaviors of prostate cancer cells through microRNA-5787 and its multiple target genes such as WWOX and FLNA.
利益披露 Disclosure
M. Watanabe, None..
H. Nakano, None..
Y. Hirokawa, None..
K. Iijima, None..
Y. NIshimura, None.