Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 124, Issue 12, Pages 2771-2779Publisher
WILEY
DOI: 10.1002/ijc.24349
Keywords
TGF-beta; cancer stem cell; invasion; metastasis; E-cadherin
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Funding
- Japanese Ministry of Education, Scientific and Culture of Japan
- Grants-in-Aid for Scientific Research [21390062] Funding Source: KAKEN
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We report here side population (SP) cells, a cancer stein 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-beta, 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-beta 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-beta treatment, whereas NIP cells did not respond to TGF-beta-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. (C) 2009 UICC
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