Department of Histology and Embryology, Poznan University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, Poland.
Department of Nursing, Poznan University of Medical Sciences, Smoluchowskiego 11 St., 60-179 Poznań, Poland.
Int J Mol Sci. 2018 Dec 23;20(1):54. doi: 10.3390/ijms20010054.
A major contributor leading to treatment failure of ovarian cancer patients is the drug resistance of cancer cell. CSCs- (cancer stem cells) and ECM (extracellular matrix)-related models of drug resistance are described as independently occurring in cancer cells. Lysyl oxidase (LOX) is another extracellular protein involved in collagen cross-linking and remodeling of extracellular matrix and has been correlated with tumor progression. The expression of LOX, COL1A2, COL3A1, and ALDH1A1 was performed in sensitive (A2780, W1) and resistant to paclitaxel (PAC) (A2780PR1 and W1PR2) and topotecan (TOP) (W1TR) cell lines at the mRNA (real-time PCR analysis) and protein level (Western blot and immunofluorescence analysis). The ALDH1A1 activity was measured with the ALDEFLUOR test and flow cytometry analysis. The protein expression in ovarian cancer tissues was determined by immunohistochemistry. We observed an increased expression of LOX and collagens in PAC and TOP resistant cell lines. Subpopulations of ALDH1A1 positive and negative cells were also noted for examined cell lines. Additionally, the coexpression of LOX with ALDH1A1 and COL1A2 with ALDH1A1 was observed. The expression of LOX, collagens, and ALDH1A1 was also detected in ovarian cancer lesions. In our study LOX, ALDH1A1 and collagens were found to be coordinately expressed by cells resistant to PAC (LOX, ALDH1A1, and COL1A2) or to TOP (LOX and ALDH1A1). This represents the study where molecules related with CSCs (ALDH1A1) and ECM (LOX, collagens) models of drug resistance are described as occurring simultaneously in ovarian cancer cells treated with PAC and TOP.
导致卵巢癌患者治疗失败的一个主要因素是癌细胞的耐药性。CSCs（癌症干细胞）和 ECM（细胞外基质）相关的耐药模型被描述为独立发生在癌细胞中。赖氨酰氧化酶（LOX）是另一种参与细胞外基质胶原交联和重塑的细胞外蛋白，与肿瘤进展相关。在对紫杉醇（PAC）（A2780PR1 和 W1PR2）和拓扑替康（TOP）（W1TR）耐药的敏感（A2780、W1）细胞系中，进行了 LOX、COL1A2、COL3A1 和 ALDH1A1 的表达，在 mRNA（实时 PCR 分析）和蛋白质水平（Western blot 和免疫荧光分析）。用 ALDEFLUOR 试验和流式细胞术分析测定 ALDH1A1 活性。通过免疫组织化学测定卵巢癌组织中的蛋白质表达。我们观察到在 PAC 和 TOP 耐药细胞系中 LOX 和胶原蛋白的表达增加。还观察到被检查的细胞系中存在 ALDH1A1 阳性和阴性细胞亚群。此外，还观察到 LOX 与 ALDH1A1 的共表达以及 COL1A2 与 ALDH1A1 的共表达。在卵巢癌病变中也检测到 LOX、胶原蛋白和 ALDH1A1 的表达。在我们的研究中，发现对 PAC（LOX、ALDH1A1 和 COL1A2）或 TOP（LOX 和 ALDH1A1）耐药的细胞中 LOX、ALDH1A1 和胶原蛋白协同表达。这代表了研究中描述的与 CSCs（ALDH1A1）和 ECM（LOX、胶原蛋白）耐药模型相关的分子同时发生在接受 PAC 和 TOP 治疗的卵巢癌细胞中。
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