RRC ID 57881
Author Shichi Y, Sasaki N, Michishita M, Hasegawa F, Matsuda Y, Arai T, Gomi F, Aida J, Takubo K, Toyoda M, Yoshimura H, Takahashi K, Ishiwata T.
Title Enhanced morphological and functional differences of pancreatic cancer with epithelial or mesenchymal characteristics in 3D culture.
Journal Sci Rep
Abstract Pancreatic cancer, composed of heterogeneous cancer cells, alters epithelial to mesenchymal features during growth and metastasis. In this study, we aimed to characterize pancreatic ductal adenocarcinoma (PDAC) cells showing epithelial or mesenchymal features in 3D culture. In 3D culture, PK-1 cells had high E-cadherin and low vimentin expression and exhibited a round-like appearance encircled by flat cells. PANC-1 cells had high vimentin and low E-cadherin expression and formed grape-like spheres. PK-1 cells had secretary granules and many microvilli, desmosomes, and adherens junctions, while PANC-1 cells had few microvilli, adherens junction, and no desmosomes. Cytokeratin 7, trypsin, CA19-9, and E-cadherin were highly expressed in PK-1 cells but not in PANC-1 cells. Ki-67 was diffusely expressed in PANC-1 spheres but was restricted to the peripheral flat cells of PK-1 spheres. PANC-1 and PK-1 cells were positive for transforming growth factor (TGF) β receptor II and phosphorylated smad2/3, but PK-1 cells were smad4 negative. Taken together, 3D culture enhanced morphofunctional differences of PDAC cells showing epithelial or mesenchymal characteristics, and epithelial phenotype maintenance may be due to the ineffectiveness of the TGF- β pathway. Clarification of heterogeneity using 3D culture may be useful for development of individualized diagnostic and therapeutic methods in patients with PDAC.
Volume 9(1)
Pages 10871
Published 2019-7-26
DOI 10.1038/s41598-019-47416-w
PII 10.1038/s41598-019-47416-w
PMID 31350453
PMC PMC6659675
MeSH Antigens, Tumor-Associated, Carbohydrate / metabolism Cadherins / metabolism Carcinoma, Pancreatic Ductal / pathology* Cell Culture Techniques Cell Line, Tumor Cell Movement Cell Shape Cell Transformation, Neoplastic Desmosomes / metabolism* Epithelial Cells / pathology* Epithelial-Mesenchymal Transition Gene Expression Regulation, Neoplastic Humans Keratin-7 / metabolism Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology* Signal Transduction Transforming Growth Factor beta / metabolism Vimentin / metabolism
IF 3.998
Times Cited 4
Resource
Human and Animal Cells T3M-4(RCB1021)