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建立并鉴定新型高侵袭性 HER2 阳性和三阴性乳腺癌细胞系。

Establishment and characterization of novel highly aggressive HER2‑positive and triple‑negative breast cancer cell lines.

机构信息

Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

出版信息

Oncol Rep. 2021 Dec;46(6). doi: 10.3892/or.2021.8205. Epub 2021 Oct 15.

Abstract

Breast cancer cell lines are widely used as an system with which to study the mechanisms underlying biological and chemotherapeutic resistance. In the present study, two novel breast cancer cell lines designated as PC‑B‑142CA and PC‑B‑148CA were successfully established from HER2‑positive and triple‑negative (TN) breast cancer tissues. The cell lines were characterized by cytokeratin (CK), α‑smooth muscle actin (α‑SMA), fibroblast‑activation protein (FAP) and programmed death‑ligand 1 (PD‑L1). Cell proliferation was assessed using a colony formation assay, an MTS assay, 3‑dimensional (3‑D) spheroid and 3‑D organoid models. Wound healing and Transwell migration assays were used to explore the cell migration capability. The responses to doxorubicin (DOX) and paclitaxel (PTX) were evaluated by 3‑D spheroids. The results showed that the PC‑B‑142CA and PC‑B‑148CA cell lines were α‑SMA‑negative, FAP‑negative, CK‑positive and PD‑L1‑positive. Both cell lines were adherent with the ability of 3‑D‑multicellular spheroid and organoid formations; invadopodia were found in the spheroids/organoids of only PC‑B‑148CA. PC‑B‑142CA had a faster proliferative but lower metastatic rate compared to PC‑B‑148CA. Compared to MDA‑MB‑231, a commercial TN breast cancer cell line, PC‑B‑148CA had a similar CD44/CD24 stemness property (96.90%), whereas only 8.75% were found in PC‑B‑142CA. The mutations of , and were found in PC‑B‑142CA cells related to the resistance of several drugs, whereas PC‑B‑148CA had mutated and . In conclusion, PC‑B‑142CA can serve as a novel HER2‑positive breast cancer cell line for drug resistance studies; while PC‑B‑148CA is a novel TN breast cancer cell line suitable for metastatic and stemness‑related properties.

摘要

乳腺癌细胞系被广泛用作研究生物和化学耐药机制的 系统。在本研究中,从 HER2 阳性和三阴性(TN)乳腺癌组织中成功建立了两个新的乳腺癌细胞系,命名为 PC-B-142CA 和 PC-B-148CA。这些细胞系通过细胞角蛋白(CK)、α-平滑肌肌动蛋白(α-SMA)、成纤维细胞激活蛋白(FAP)和程序性死亡配体 1(PD-L1)进行鉴定。通过集落形成实验、MTS 测定、三维(3-D)球体和 3-D 类器官模型评估细胞增殖。使用划痕愈合和 Transwell 迁移实验来探索细胞迁移能力。通过 3-D 球体评估对阿霉素(DOX)和紫杉醇(PTX)的反应。结果表明,PC-B-142CA 和 PC-B-148CA 细胞系为 α-SMA 阴性、FAP 阴性、CK 阳性和 PD-L1 阳性。两种细胞系均具有贴壁性,具有 3-D 多细胞球体和类器官形成的能力;仅在 PC-B-148CA 的球体/类器官中发现有侵袭伪足。与 PC-B-148CA 相比,PC-B-142CA 的增殖速度更快,但迁移率更低。与商业性 TN 乳腺癌细胞系 MDA-MB-231 相比,PC-B-148CA 具有相似的 CD44/CD24 干性特征(96.90%),而在 PC-B-142CA 中仅发现 8.75%。在与几种药物耐药相关的 PC-B-142CA 细胞中发现了 、 和 的突变,而 PC-B-148CA 则发生了 和 的突变。总之,PC-B-142CA 可作为研究耐药性的新型 HER2 阳性乳腺癌细胞系;而 PC-B-148CA 是一种新型 TN 乳腺癌细胞系,适合用于转移和干性相关特性的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/252f/8548790/d0d703e62838/or-46-06-08205-g00.jpg

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