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Jing Mo,
Baocun Sun,
Xiulan Zhao,
Qiang Gu, Xueyi Dong,
Zhiyong Liu,
Yuemei Ma,
Nan Zhao,
Yanrong Liu,
Jiadong Chi,
Ran Sun
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ABSTRACT: Cancer stem cells (CSCs) have been identified in various malignancies, and different properties have been examined to characterize CSCs: tumorigenicity in immunocompromised mice, stem cell surface markers, label-retaining properties, and proliferation as nonadherent spheres. This study explored the consistency and efficiency among these methods. Among the melanoma cell lines examined (A375, A875, MUM-2b, and MUM-2c), only A375 and MUM-2c grew as nonadherent spheres and continuously propagated in a defined serum-free medium in vitro. Flow cytometry and immunofluorescence analysis indicated that sphere-derived cells contained a smaller proportion of cells expressing the candidate surface markers of melanoma stem cells such as ABCB5, CD133, CD20 and CD271, and a larger proportion of cells expressing melanocytic differentiation markers such as HMB45 and S100 protein, compared with adherent cells. Surprisingly, the more highly differentiated sphere-derived melanoma cells exhibited increased tumorigenic potential in vivo, as indicated by shorter tumor incubation (A375) and smaller number of cells required to initiate tumor formation (A375 and MUM-2c) compared with those of parental cells. Despite the similarity in histopathological characteristics, the expression profile indicated that xenografts derived from sphere-derived melanoma cells exhibited a more tumorigenic phenotype with respect to the stem or the differentiation markers detected by immunohistochemical analysis. Therefore, sphere formation in nonadherent cultures may not be a preferred surrogate in-vitro method for enriching melanoma stem cells according to candidate markers but may be a favorable condition for activating potential CSCs.
Melanoma research 06/2013; · 2.06 Impact Factor
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Tieju Liu,
Baocun Sun,
Xiulan Zhao,
Qiang Gu, Xueyi Dong,
Zhi Yao,
Nan Zhao,
Jiadong Chi,
Ning Liu,
Ran Sun,
Yuemei Ma
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ABSTRACT: Vasculogenic mimicry (VM) refers to the condition in which tumour cells mimic endothelial cells to form extracellular matrix-rich tubular channels. VM is more extensive in more aggressive tumours. The human epidermal growth factor receptor 2 (HER2) gene is amplified in 20-30% of human breast cancers and has been implicated in mediating aggressive tumour growth and metastasis. However, thus far, there have been no data on the role of HER2 in VM formation. Immunohistochemical and histochemical double-staining methods were performed to display VM in breast cancer specimens. Transfection in MCF7 cells was performed and clones were selected by G418. The three-dimensional Matrigel culture was used to evaluate VM formation in the breast cancer cell line. According to statistical analysis, VM was related to the presence of a positive nodal status and advanced clinical stage. The positive rate of VM increased with increased HER2 expression. In addition, cases with HER2 3+ expression showed significantly greater VM channel count than those in other cases. The exogenous HER2 overexpression in MCF-7 cells induced vessel-like VM structures on the Matrigel and increased the VM mediator vascular endothelial (VE) cadherin. Our data provide evidence for a clinically relevant association between HER2 and VM in human invasive breast cancer. HER2 overexpression possibly induces VM through the up-regulation of VE cadherin. Understanding the key molecular events may provide therapeutic intervention strategies for HER2+ breast cancer.
Journal of Cellular and Molecular Medicine 12/2012; · 4.13 Impact Factor
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ABSTRACT: Triple-negative breast cancer, which is negative for the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, represents about 15-26% of all breast cancer cases. However, because of its genotype, a triple-negative disease accounts for a remarkable metastasis and mortality. Moreover, no targeted treatment is available because the molecular mechanism of triple-negative breast cancer initiation is still unclear. Secreted clusterin (sCLU) is associated with the refractory to anti-estrogen in breast cancer cells. We investigated the sCLU expression in 384 human breast cancer cases, including 61 triple-negative cases, as well as the relationship between sCLU and clinical pathological characteristics. Triple-negative patients (75.4%) were positive for sCLU based on immunohistochemical analysis, and sCLU expression in this subtype was proven related to a larger tumor size, an axillary node status, and a higher clinical stage. Furthermore, we used a spontaneous breast cancer mouse strain with a triple-negative genotype to detect the sCLU dynamic expression in breast cancer oncogenesis using western blot and real-time polymerase chain reaction. The sCLU mRNA and protein expression in the tumor and hyperplastic epithelium were upregulated and reached a peak compared with those of a normal mammary gland. These results suggest that sCLU is involved in the initiation of triple-negative breast cancer, which is beneficial for the clinical trial design of an anti-CLU treatment for triple-negative breast cancer.
Cancer biology & therapy 03/2012; 13(5):321-9. · 2.64 Impact Factor
