Transmission electron microscopic analysis of pancreatic ductal adenocarcinoma cell spheres formed in 3D cultures.

IF 1.2 4区医学 Q3 PATHOLOGY

Medical Molecular Morphology Pub Date : 2025-04-04 DOI:10.1007/s00795-025-00435-1

Yuuki Shichi, Masakazu Fujiwara, Fujiya Gomi, Keisuke Nonaka, Fumio Hasegawa, Seiichi Shinji, Hirofumi Rokutan, Tomio Arai, Kimimasa Takahashi, Toshiyuki Ishiwata

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) cell lines are classified into two types: epithelial and mesenchymal protein-expressing. Using scanning electron microscopy, we reported that these two groups differ in terms of morphology when they formed tumor spheres under three-dimensional (3D) culturing. In this study, we used transmission electron microscopy (TEM) to examine the intracellular microstructures of five epithelial and three mesenchymal PDAC cell lines in 3D culture, and compared them to the morphologies of the same cell types in two-dimensional (2D) cultures. Microvilli were present in all PDAC cells cultured in 2D and 3D, and were well developed in epithelial PDAC cells. Desmosome-like structures were only observed in epithelial PDAC cells, and were more common in 3D cultures. Secretory granules were observed in epithelial PDAC and mesenchymal PANC-1 cells, and were more common in 3D cultures. Intracytoplasmic lumina were only observed in epithelial PK-59 and T3M-4 cells cultured in 3D. Abundant filamentous aggregates were observed in 2D-cultured T3M-4 and MIA PaCa-2 cells. By contrast, entosis was observed in 3D-cultured PK-59, PK-1, and KP4 cells. Microstructural differences enhanced by 3D culturing revealed significant phenotypic diversity among PDAC cells, and may provide key insights into curing intractable pancreatic cancer.

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对三维培养中形成的胰腺导管腺癌细胞球进行透射电子显微镜分析。

胰腺导管腺癌（Pancreatic ductal adencarcinoma， PDAC）细胞系分为表达上皮蛋白和表达间充质蛋白两种类型。利用扫描电镜，我们报道了这两组在三维（3D）培养下形成肿瘤球时的形态学差异。在这项研究中，我们使用透射电子显微镜（TEM）检查了5种上皮细胞和3种间充质PDAC细胞系在3D培养中的细胞内微观结构，并将其与相同细胞类型在二维（2D）培养中的形态进行了比较。微绒毛存在于2D和3D培养的PDAC细胞中，并且在上皮PDAC细胞中发育良好。桥粒样结构仅在上皮PDAC细胞中观察到，在3D培养中更为常见。在上皮细胞PDAC和间充质细胞PANC-1中观察到分泌颗粒，在3D培养中更常见。仅在3D培养的上皮细胞PK-59和T3M-4中观察到胞浆内腔。在二维培养的T3M-4和MIA PaCa-2细胞中观察到丰富的丝状聚集体。相比之下，3d培养的PK-59、PK-1和KP4细胞出现内吞现象。3D培养增强的微观结构差异揭示了PDAC细胞之间显着的表型多样性，并可能为治疗难治性胰腺癌提供关键见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medical Molecular Morphology 医学-病理学

CiteScore

2.90

自引率

5.60%

发文量

审稿时长

>12 weeks

期刊介绍： Medical Molecular Morphology is an international forum for researchers in both basic and clinical medicine to present and discuss new research on the structural mechanisms and the processes of health and disease at the molecular level. The structures of molecules, organelles, cells, tissues, and organs determine their normal function. Disease is thus best understood in terms of structural changes in these different levels of biological organization, especially in molecules and molecular interactions as well as the cellular localization of chemical components. Medical Molecular Morphology welcomes articles on basic or clinical research in the fields of cell biology, molecular biology, and medical, veterinary, and dental sciences using techniques for structural research such as electron microscopy, confocal laser scanning microscopy, enzyme histochemistry, immunohistochemistry, radioautography, X-ray microanalysis, and in situ hybridization. Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.