This study was designed to investigate the invasion of human papillomavirus (HPV) positive human cervical carcinoma cell lines in human leiomyoma-based extracellular matrices in vitro, and to test the suitability of the model for studying the irradiation effects on the cancer cell invasion. HPV positive cervical carcinoma cell lines SiHa and CaSki, and HPV negative squamous cell carcinoma cell line HSC-3 were used. CaSki cells contain around 600 copies of HPV 16 virus in the genome, whereas SiHa have only 1–2 copies per cell. Cells were analyzed using two different human tumor derived extracellular matrix methods (3D myoma disc model, and Myogel Transwell invasion assay). Cultures were irradiated with 4 Gy. Myoma invasion area and the depth of invasion were measured with ImageJ 1.51j8 software. Statistical analyses were performed with SPSS Statistics (IBM SPSS® Statistics 25). All cells invaded through Myogel coated Transwell membranes and within myoma discs. In myoma discs, a difference in the invasion depth (p = 0.0001) but not in invasion area (p = 0.310) between the HPV positive cell lines was seen, since SiHa (less HPV) invaded slightly better than CaSki (more HPV). HSC-3 cells (HPV negative) invaded deepest (p = 0.048) than either of the HPV positive cell line cells. No difference was detected in the invasion area (p = 0.892) between HPV positive and HPV negative cells. The ionized radiation significantly reduced the invasion depth of HSC-3 (p = 0.008), SiHa (p = 0.0001) and CaSki (p = 0.005). No significant effect on the invasion area was detected in any of the cell lines. However, a significant difference was observed between SiHa and CaSki in the reduction of the invasion depth after radiation (p = 0.013) as the reduction was greater with SiHa than CaSki. Both solid and gelatinous human leiomyoma-based extracellular matrix models were suitable platforms to study the invasion of HPV positive cervical carcinoma cells in vitro. SiHa cells with less HPV copy number cells invaded slightly better and were slightly more sensitive to irradiation than CaSki cells with high HPV copy number. However, there was no drastic differences between the invasion properties of these carcinoma cells.

中文翻译：

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基于人肌瘤组织的细胞外基质模型，用于测试辐射对HPV阳性细胞的影响。

本研究旨在研究人乳头瘤病毒（HPV）阳性人宫颈癌细胞系在体外基于人平滑肌瘤的细胞外基质中的侵袭，并检验该模型对研究辐射对癌细胞侵袭的适应性。使用HPV阳性宫颈癌细胞系SiHa和CaSki，以及HPV阴性鳞状细胞癌细胞系HSC-3。CaSki细胞在基因组中包含大约600个HPV 16病毒拷贝，而SiHa每个细胞只有1-2个拷贝。使用两种不同的人类肿瘤衍生的细胞外基质方法（3D肌瘤椎间盘模型和Myogel Transwell入侵测定法）分析细胞。用4 Gy照射培养物。用ImageJ 1.51j8软件测量肌瘤浸润面积和浸润深度。使用SPSS Statistics（IBMSPSS®Statistics 25）进行统计分析。所有细胞均通过Myogel涂层的Transwell膜和肌瘤盘侵入。在肌瘤盘中，发现HPV阳性细胞系之间的浸润深度（p = 0.0001）而不是浸润区域（p = 0.310）有所不同，因为SiHa（HPV较少）的侵袭性略好于CaSki（HPV较多）。HSC-3细胞（HPV阴性）比任何一个HPV阳性细胞系侵袭最深（p = 0.048）。在HPV阳性和HPV阴性细胞之间，在侵袭区域未检测到差异（p = 0.892）。电离辐射显着降低了HSC-3（p = 0.008），SiHa（p = 0.0001）和CaSki（p = 0.005）的浸润深度。在任何细胞系中均未检测到对侵袭区域的显着影响。然而，在SiHa和CaSki之间观察到在辐射后的浸润深度降低方面存在显着差异（p = 0.013），因为SiHa的降低大于CaSki。基于固体和胶状人平滑肌瘤的细胞外基质模型都是研究HPV阳性宫颈癌细胞体外侵袭的合适平台。与具有高HPV拷贝数的CaSki细胞相比，具有较少HPV拷贝数的细胞的SiHa细胞侵入性更好，对辐射的敏感性稍高。但是，这些癌细胞的侵袭特性之间没有显着差异。基于固体和胶状人平滑肌瘤的细胞外基质模型都是研究HPV阳性宫颈癌细胞体外侵袭的合适平台。与具有高HPV拷贝数的CaSki细胞相比，具有较少HPV拷贝数的细胞的SiHa细胞侵入性更好，对辐射的敏感性稍高。但是，这些癌细胞的侵袭特性之间没有显着差异。基于固体和胶状人平滑肌瘤的细胞外基质模型都是研究HPV阳性宫颈癌细胞体外侵袭的合适平台。与具有高HPV拷贝数的CaSki细胞相比，具有较少HPV拷贝数的细胞的SiHa细胞侵入性更好，对辐射的敏感性稍高。但是，这些癌细胞的侵袭特性之间没有显着差异。