title: A critical role of CD29 and CD49f in mediating metastasis for cancer-initiating cells isolated from a Brca1-associated mouse model of breast cancer.
abstract: Cancer metastasis is a lethal problem that claims the lives of over 90% of cancer patients. In this study, we have investigated metastatic potential of cancer stem cells (CSCs) isolated from mammary tumors of a Brca1-mutant mouse model. Our data indicated that CSCs, which are enriched in CD24(+)CD29(+)/CD49f(+) cell population, displayed much higher migration ability than CD24(-)CD29(-)/CD49f(-) cells in tissue culture and enhanced metastatic potential in allograft-nude mice. CD24(+)CD29(+) cells maintained the ability to differentiate and reconstitute heterogeneity in the metastatic tumors whereas CD24(-)CD29(-) cells could not. Corresponding to their enhanced metastatic ability, CD24(+)CD29(+) cells exhibited features of the epithelial to mesenchymal transition. Finally, using short hairpin RNA to knock down CD29 and/or CD49f in metastatic cancer cells, we demonstrated that while acute knockdown of CD29 or CD49f alone slightly decreased cell migration ability, knockdown of both genes generated a profound effect to block their migration, revealing an overlapping, yet critical function of both genes in the migration of CSCs. Our findings indicate that in addition to serving as markers of CSCs, CD29 and CD49f may also serve as potential therapeutic targets for cancer metastasis.
authors: Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA.
authors: A
authors: A
authors: Vassilopoulos
authors: Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA.
authors: C
authors: C
authors: Chisholm
authors: Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA.
authors: T
authors: T
authors: Lahusen
authors: Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA.
authors: H
authors: H
authors: Zheng
authors: Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA.
authors: C-X
authors: CX
authors: Deng
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor; D051927:CD24 Antigen / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D008819:Mice, Nude; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D039503:Integrin alpha6; D054411:Receptors, Leptin; C515447:leptin receptor, mouse