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Side population of pancreatic cancer cells predominates in TGF‐β‐mediated epithelial to mesenchymal transition and invasion
Author(s) -
Kabashima Ayano,
Higuchi Hajime,
Takaishi Hiromasa,
Matsuzaki Yumi,
Suzuki Sadafumi,
Izumiya Motoko,
Iizuka Hideko,
Sakai Gen,
Hozawa Shigenari,
Azuma Toshifumi,
Hibi Toshifumi
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24349
Subject(s) - epithelial–mesenchymal transition , matrigel , metastasis , pancreatic cancer , biology , cancer stem cell , cancer cell , population , mesenchymal stem cell , cancer research , cell culture , side population , cell , cancer , stem cell , microbiology and biotechnology , medicine , angiogenesis , genetics , environmental health
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. © 2008 UICC