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Article

Electron microscopic analysis of different cell types in human pancreatic cancer spheres

  • Authors:
    • Toshiyuki Ishiwata
    • Fumio Hasegawa
    • Masaki Michishita
    • Norihiko Sasaki
    • Naoshi Ishikawa
    • Kaiyo Takubo
    • Yoko Matsuda
    • Tomio Arai
    • Junko Aida
  • View Affiliations / Copyright

    Affiliations: Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173‑0015, Japan, Department of Veterinary Pathology, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo 180‑8602, Japan, Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Tokyo 173‑0015, Japan, Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo 173‑0015, Japan
  • Pages: 2485-2490
    |
    Published online on: December 8, 2017
       https://doi.org/10.3892/ol.2017.7554
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Abstract

Cancer stem cells (CSCs), which are pluripotent and self‑renewable, contribute to the initiation and metastasis of cancer, and are responsible for resistance to chemotherapy and radiation. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer that is associated with a high incidence of distant metastasis and recurrence. Sphere formation reveals cell proliferation under nonadherent conditions and is commonly used to identify CSCs; measurements of the number, area and volume of the spheres are used to estimate stemness of PDAC cells. However, detailed morphological analysis of such spheres has not been performed. The aim of the present study was to examine the morphology of spheres isolated from PANC‑1 human pancreatic cancer cells via scanning electron microscopy (SEM) and transmission electron microscopy (TEM). PANC‑1 cells formed round to irregular oblong spheres within 1 week following seeding in ultra‑low‑attachment plates. These spheres exhibited higher levels of expression of CSC markers, including nestin, sex determining region Y‑box 2, and CD44 containing variant exon 9, compared with adherent cells. SEM analysis revealed that the spheres exhibited a grape‑like appearance, harboring cancer cells with smooth or rough surfaces. Similarly, TEM analysis detected cancer cells with varying surface types within the spheres: Those with smooth surfaces, irregular large protrusions, protrusions and a small number of microvilli, and those with many microvilli throughout the entire cell surface. These morphological differences among cancer cells may be indicative of different stages in the differentiation process, from CSCs to non‑CSCs, within the spheres.
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View References

1 

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM and Matrisian LM: Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver and pancreas cancers in the United States. Cancer Res. 74:2913–2921. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL and Wahl GM: Cancer stem cells-perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res. 66:9339–9344. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Lonardo E, Hermann PC and Heeschen C: Pancreatic cancer stem cells-update and future perspectives. Mol Oncol. 4:431–442. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Reya T, Morrison SJ, Clarke MF and Weissman IL: Stem cells, cancer and cancer stem cells. Nature. 414:105–111. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Matsuda Y, Kure S and Ishiwata T: Nestin and other putative cancer stem cell markers in pancreatic cancer. Med Mol Morphol. 45:59–65. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Ishiwata T: Cancer stem cells and epithelial-mesenchymal transition: Novel therapeutic targets for cancer. Pathol Int. 66:601–608. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Gou S, Liu T, Wang C, Yin T, Li K, Yang M and Zhou J: Establishment of clonal colony-forming assay for propagation of pancreatic cancer cells with stem cell properties. Pancreas. 34:429–435. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Gaviraghi M, Tunici P, Valensin S, Rossi M, Giordano C, Magnoni L, Dandrea M, Montagna L, Ritelli R, Scarpa A and Bakker A: Pancreatic cancer spheres are more than just aggregates of stem marker-positive cells. Biosci Rep. 31:45–55. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Yin T, Wei H, Gou S, Shi P, Yang Z, Zhao G and Wang C: Cancer stem-like cells enriched in Panc-1 spheres possess increased migration ability and resistance to gemcitabine. Int J Mol Sci. 12:1595–1604. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Michishita M, Akiyoshi R, Yoshimura H, Katsumoto T, Ichikawa H, Ohkusu-Tsukada K, Nakagawa T, Sasaki N and Takahashi K: Characterization of spheres derived from canine mammary gland adenocarcinoma cell lines. Res Vet Sci. 91:254–260. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Matsuda Y, Ishiwata T, Yoshimura H, Yamashita S, Ushijima T and Arai T: Systemic administration of small interfering RNA targeting human nestin inhibits pancreatic cancer cell proliferation and metastasis. Pancreas. 45:93–100. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Matsuda Y, Yoshimura H, Ueda J, Naito Z, Korc M and Ishiwata T: Nestin delineates pancreatic cancer stem cells in metastatic foci of NOD/Shi-scid IL2Rγ (null) (NOG) mice. Am J Pathol. 184:674–685. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Konings J, Hoving LR, Ariens RS, Hethershaw EL, Ninivaggi M, Hardy LJ, de Laat B, Ten Cate H, Philippou H and Govers-Riemslag JW: The role of activated coagulation factor XII in overall clot stability and fibrinolysis. Thromb Res. 136:474–480. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Schurgers E, Moorlag M, Hemker C, Lindhout T, Kelchtermans H and de Laat B: Thrombin generation in zebrafish blood. PLoS One. 11:e01491352016. View Article : Google Scholar : PubMed/NCBI

17 

Sharma N, Nanta R, Sharma J, Gunewardena S, Singh KP, Shankar S and Srivastava RK: PI3K/AKT/mTOR and sonic hedgehog pathways cooperate together to inhibit human pancreatic cancer stem cell characteristics and tumor growth. Oncotarget. 6:32039–32060. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Herreros-Villanueva M, Zhang JS, Koenig A, Abel EV, Smyrk TC, Bamlet WR, de Narvajas AA, Gomez TS, Simeone DM, Bujanda L and Billadeau DD: SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells. Oncogenesis. 2:e612013. View Article : Google Scholar : PubMed/NCBI

19 

Kiuchi S, Ikeshita S, Miyatake Y and Kasahara M: Pancreatic cancer cells express CD44 variant 9 and multidrug resistance protein 1 during mitosis. Exp Mol Pathol. 98:41–46. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Breslin S and O'Driscoll L: The relevance of using 3D cell cultures, in addition to 2D monolayer cultures, when evaluating breast cancer drug sensitivity and resistance. Oncotarget. 7:45745–45756. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Ishiwata T, Teduka K, Yamamoto T, Kawahara K, Matsuda Y and Naito Z: Neuroepithelial stem cell marker nestin regulates the migration, invasion and growth of human gliomas. Oncol Rep. 26:91–99. 2011.PubMed/NCBI

22 

Ware MJ, Colbert K, Keshishian V, Ho J, Corr SJ, Curley SA and Godin B: Generation of homogenous three-dimensional pancreatic cancer cell spheroids using an improved hanging drop technique. Tissue Eng Part C Methods. 22:312–321. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Bez A, Corsini E, Curti D, Biggiogera M, Colombo A, Nicosia RF, Pagano SF and Parati EA: Neurosphere and neurosphere-forming cells: Morphological and ultrastructural characterization. Brain Res. 993:18–29. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Gage FH: Mammalian neural stem cells. Science. 287:1433–1438. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Ilieva M and Dufva M: SOX2 and OCT4 mRNA-expressing cells, detected by molecular beacons, localize to the center of neurospheres during differentiation. PLoS One. 8:e736692013. View Article : Google Scholar : PubMed/NCBI

26 

Suslov ON, Kukekov VG, Ignatova TN and Steindler DA: Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres. Proc Natl Acad Sci USA. 99:pp. 14506–14511. 2002; View Article : Google Scholar : PubMed/NCBI

27 

Bhagwandin VJ and Shay JW: Pancreatic cancer stem cells: Fact or fiction? Biochim Biophys Acta. 1792:248–259. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Hruban RH, Pitman MB and Klimstra DS: Ductal adenocarcinoma(Tumors of the Pancreas. Atlas of Tumor Pathology, 4th series). Silverberg SG and Sobin LH: American Registry of Pathology. Washington, DC: pp. 111–164. 2007

29 

Lu Y, Onda M, Uchida E, Yamamura S, Yanagi K, Matsushita A, Kobayashi T, Fukuhara M, Aida K and Tajiri T: The cytotoxic effects of bile acids in crude bile on human pancreatic cancer cell lines. Surg Today. 30:903–909. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Tammela T, Sanchez-Rivera FJ, Cetinbas NM, Wu K, Joshi NS, Helenius K, Park Y, Azimi R, Kerper NR, Wesselhoeft RA, et al: A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature. 545:355–359. 2017. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ishiwata T, Hasegawa F, Michishita M, Sasaki N, Ishikawa N, Takubo K, Matsuda Y, Arai T and Aida J: Electron microscopic analysis of different cell types in human pancreatic cancer spheres. Oncol Lett 15: 2485-2490, 2018.
APA
Ishiwata, T., Hasegawa, F., Michishita, M., Sasaki, N., Ishikawa, N., Takubo, K. ... Aida, J. (2018). Electron microscopic analysis of different cell types in human pancreatic cancer spheres. Oncology Letters, 15, 2485-2490. https://doi.org/10.3892/ol.2017.7554
MLA
Ishiwata, T., Hasegawa, F., Michishita, M., Sasaki, N., Ishikawa, N., Takubo, K., Matsuda, Y., Arai, T., Aida, J."Electron microscopic analysis of different cell types in human pancreatic cancer spheres". Oncology Letters 15.2 (2018): 2485-2490.
Chicago
Ishiwata, T., Hasegawa, F., Michishita, M., Sasaki, N., Ishikawa, N., Takubo, K., Matsuda, Y., Arai, T., Aida, J."Electron microscopic analysis of different cell types in human pancreatic cancer spheres". Oncology Letters 15, no. 2 (2018): 2485-2490. https://doi.org/10.3892/ol.2017.7554
Copy and paste a formatted citation
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Spandidos Publications style
Ishiwata T, Hasegawa F, Michishita M, Sasaki N, Ishikawa N, Takubo K, Matsuda Y, Arai T and Aida J: Electron microscopic analysis of different cell types in human pancreatic cancer spheres. Oncol Lett 15: 2485-2490, 2018.
APA
Ishiwata, T., Hasegawa, F., Michishita, M., Sasaki, N., Ishikawa, N., Takubo, K. ... Aida, J. (2018). Electron microscopic analysis of different cell types in human pancreatic cancer spheres. Oncology Letters, 15, 2485-2490. https://doi.org/10.3892/ol.2017.7554
MLA
Ishiwata, T., Hasegawa, F., Michishita, M., Sasaki, N., Ishikawa, N., Takubo, K., Matsuda, Y., Arai, T., Aida, J."Electron microscopic analysis of different cell types in human pancreatic cancer spheres". Oncology Letters 15.2 (2018): 2485-2490.
Chicago
Ishiwata, T., Hasegawa, F., Michishita, M., Sasaki, N., Ishikawa, N., Takubo, K., Matsuda, Y., Arai, T., Aida, J."Electron microscopic analysis of different cell types in human pancreatic cancer spheres". Oncology Letters 15, no. 2 (2018): 2485-2490. https://doi.org/10.3892/ol.2017.7554
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