Side population of pancreatic cancer cells predominates in TGF-β-mediated epithelial to mesenchymal transition and invasion

Ayano Kabashima, Hajime Higuchi, Hiromasa Takaishi, Yumi Matsuzaki, Sadafumi Suzuki, Motoko Izumiya, Hideko Iizuka, Gen Sakai, Shigenari Hozawa, Toshifumi Azuma, Toshifumi Hibi

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

We report here side population (SP) cells, a cancer stem cell enriched fraction from pancreatic cancer cell line, have enormous superior potential of the epithelial to mesenchymal transition (EMT), invasion, and metastasis. In an isolated SP cell culture, the cells rapidly expressed and up-regulated E-cadherin, an epithelial phenotypic marker, and the cells formed tightly contacted cell cluster, which is a representative epithelial phenotypic appearance. When the SP cells were incubated in the presence of TGF-β, SP cells changed their shape into mesenchymal-like appearance including spindle shaped assembly. This alteration was associated with significant reduction of E-cadherin expression level. TGF-β induced EMT-associated gene alteration such as reduction of E-cadherin mRNA and induction of Snail mRNA and matrixmetalloproteinase (MMP)-2 mRNA. Finally, SP cells exerted notable matrigel invasion activity in response to TGF-β treatment, whereas MP cells did not respond to TGF-β-mediated invasion. In conclusion, these results suggest that SP cells from pancreatic cancer cell line possess superior potentials of phenotypic switch, i.e., EMT/MET, micro-invasion, and in vivo metastasis, as compared to MP cells. Because micro-invasion and metastasis are key mechanisms of cancer malignant potential, SP cells would be the attractive target for preventing cancer progression.

Original languageEnglish
Pages (from-to)2771-2779
Number of pages9
JournalInternational Journal of Cancer
Volume124
Issue number12
DOIs
Publication statusPublished - 2009 Jun 15

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Side-Population Cells
Epithelial-Mesenchymal Transition
Pancreatic Neoplasms
Population
Cadherins
Neoplasm Metastasis
Messenger RNA
Cell Line
Neoplastic Stem Cells
Snails
Neoplasms
Cell Culture Techniques

Keywords

  • Cancer stem cell
  • E-cadherin
  • Invasion
  • Metastasis
  • TGF-beta

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Side population of pancreatic cancer cells predominates in TGF-β-mediated epithelial to mesenchymal transition and invasion. / Kabashima, Ayano; Higuchi, Hajime; Takaishi, Hiromasa; Matsuzaki, Yumi; Suzuki, Sadafumi; Izumiya, Motoko; Iizuka, Hideko; Sakai, Gen; Hozawa, Shigenari; Azuma, Toshifumi; Hibi, Toshifumi.

In: International Journal of Cancer, Vol. 124, No. 12, 15.06.2009, p. 2771-2779.

Research output: Contribution to journalArticle

Kabashima, A, Higuchi, H, Takaishi, H, Matsuzaki, Y, Suzuki, S, Izumiya, M, Iizuka, H, Sakai, G, Hozawa, S, Azuma, T & Hibi, T 2009, 'Side population of pancreatic cancer cells predominates in TGF-β-mediated epithelial to mesenchymal transition and invasion', International Journal of Cancer, vol. 124, no. 12, pp. 2771-2779. https://doi.org/10.1002/ijc.24349
Kabashima, Ayano ; Higuchi, Hajime ; Takaishi, Hiromasa ; Matsuzaki, Yumi ; Suzuki, Sadafumi ; Izumiya, Motoko ; Iizuka, Hideko ; Sakai, Gen ; Hozawa, Shigenari ; Azuma, Toshifumi ; Hibi, Toshifumi. / Side population of pancreatic cancer cells predominates in TGF-β-mediated epithelial to mesenchymal transition and invasion. In: International Journal of Cancer. 2009 ; Vol. 124, No. 12. pp. 2771-2779.
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