Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage.
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, alpha-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 alpha-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.
Kato
Kiyoko
K
Department of Obstetrics and Gynecology, School of Medicine, Kyushu University, Fukuoka, Japan. kkatoh@bioreg.kyushu-u.ac.jp
Takao
Tomoka
T
Kuboyama
Ayumi
A
Tanaka
Yoshihiro
Y
Ohgami
Tatsuhiro
T
Yamaguchi
Shinichiro
S
Adachi
Sawako
S
Yoneda
Tomoko
T
Ueoka
Yousuke
Y
Kato
Keiji
K
Hayashi
Shinichi
S
Asanoma
Kazuo
K
Wake
Norio
N
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D008969:Molecular Sequence Data; D011554:Pseudopodia / Q000378:metabolism; D051381:Rats; D017154:Stromal Cells / Q000473:pathology
D000199:Actins