A novel mouse model of human breast cancer stem-like cells with high CD44+CD24-/lower phenotype metastasis to human bone / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 1980-1986, 2008.
Article
Dans Anglais
| WPRIM
| ID: wpr-350767
ABSTRACT
<p><b>BACKGROUND</b>A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel "human-source" model of human breast cancer skeletal metastasis.</p><p><b>METHODS</b>Human breast cancer stem-like cells, the CD44+/CD24-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1 x 10(5), 1 x 10(6) human breast cancer stem-like cells, and 1 x 10(6) parental MDA-MB-231 cells, respectively. A positive control group (D) without implantation of human bone was also injected with 1 x 10(6) MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 (CXCR4), and osteopontin (OPN). mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction (PCR).</p><p><b>RESULTS</b>Our results demonstrated that cells in implanted human bones of group B, which received 1 x 10(6) cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis (77.8%, P = 0.0230) and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest.</p><p><b>CONCLUSIONS</b>In the novel "human source" model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.</p>
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Anatomopathologie
/
Pharmacologie
/
Phénotype
/
Cellules souches tumorales
/
Tumeurs osseuses
/
Tumeurs du sein
/
Immunohistochimie
/
Facteur de croissance des hépatocytes
/
Antigènes CD44
/
Récepteurs CXCR4
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
/
Femelle
/
Humains
langue:
Anglais
Texte intégral:
Chinese Medical Journal
Année:
2008
Type:
Article
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