Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage

Kiyoko Kato, Tomoka Takao, Ayumi Kuboyama, Yoshihiro Tanaka, Tatsuhiro Ohgami, Shinichiro Yamaguchi, Sawako Adachi, Tomoko Yoneda, Yousuke Ueoka, Keiji Kato, Shinichi Hayashi, Kazuo Asanoma, Norio Wake

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)

Abstract

Cancer stem-like cell subpopulations, referred to as "side- population" (SP) cells, have been identified in several tumors based on their ability to efflux the fluorescent dye Hoechst 33342. Although SP cells have been identified in the normal human endometrium and endometrial cancer, little is known about their characteristics. In this study, we isolated and characterized the SP cells in human endometrial cancer cells and in rat endometrial cells expressing oncogenic human K-Ras protein. These SP cells showed i) reduction in the expression levels of differentiation markers; ii) long-term proliferative capacity of the cell cultures; iii) self-renewal capacity in vitro; iv) enhancement of migration, lamellipodia, and ,uropodia formation; and v) enhanced tumorigenicity. In nude mice, SP cells formed large, invasive tumors, which were composed of both tumor cells and stromal-like cells with enriched extracellular matrix. The expression levels of vimentin, α-smooth muscle actin, and collagen III were enhanced in SP tumors compared with the levels in non-SP tumors. In addition, analysis of microdissected samples and fluorescence in situ hybridization of Hec1-SP-tumors showed that the stromal-like cells with enriched extracellular matrix contained human DNA, confirming that the stromal-like cells were derived from the inoculated cells. Moreober, in a Matrigel assay, SP cells differentiated into α-smooth muscle actin-expressing cells. These findings demonstrate that SP cells have cancer stem-like cell features, including the potential to differentiate into the mesenchymal cell lineage.

Original languageEnglish
Pages (from-to)381-392
Number of pages12
JournalAmerican Journal of Pathology
Volume176
Issue number1
DOIs
Publication statusPublished - Jan 2010
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint

Dive into the research topics of 'Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage'. Together they form a unique fingerprint.

Cite this