Metastatic Cancer Stem Cells: An Opportunity for Improving Cancer Treatment?
ABSTRACT Many human cancers are driven by cancer stem cells (CSCs) whose connection to metastatic spread remains incompletely understood. In this issue of Cell Stem Cell, Pang et al. (2010) isolate a subpopulation of human colorectal CSCs that uniquely possesses metastatic potential.
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ABSTRACT: Drosophila can exhibit classic hallmarks of cancer, such as evasion of apoptosis, sustained proliferation, metastasis, prolonged survival, genome instability and metabolic reprogramming, when cancer-related genes are perturbed. In the last two decades studies in flies have identified several tumor suppressor and oncogenes. However, the greatest strength of the fly lies in its ability to model cancer hallmarks in a variety of tissue types, which enables the study of context-dependent tumorigenesis. We review the organs and tissues that have been used to model tumor formation, and propose new strategies to maximize the potential of Drosophila in cancer research. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.Journal of Cellular Physiology 07/2013; 229(1). DOI:10.1002/jcp.24427 · 3.87 Impact Factor
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ABSTRACT: Accumulating evidence suggests the involvement of tumor-initiating cells (T-ICs) in cancer genesis, but whether liver T-ICs contribute to HCC invasion and metastasis remains unclear. OV6(+) T-ICs were isolated from SMMC7721 and HuH7 cell lines by magnetic sorting. Characteristics of T-ICs were assessed by in vitro and mouse xenograft assays. Expression of OV6 was determined by immunostaining in specimens from 218 HCC patients, and Kaplan-Meier survival analysis was used to determine the correlation of OV6 expression with prognosis. OV6(+) T-ICs isolated from HCC cell lines not only possess a higher capacity to form tumor spheroids in vitro, but also had a greater potential to form tumors when implanted in non-obese diabetic/severe combined immunodeficient mice, suggesting their elevated self-renewal capacity and tumorigenicity. Moreover, OV6(+) T-ICs exhibited more invasive and metastatic potentials both in vitro and in vivo. Patients with more OV6(+) tumor cells were associated with aggressive clinicopathologic features and poor prognosis. CXCR4 is expressed at higher levels in OV6(+) cells. Recombinant stromal cell-derived factor-1 (SDF-1) treatment expanded the OV6(+) HCC T-ICs population, by sustaining the stem cell property of OV6(+) cells. The SDF-1 effect was blocked by a specific CXCR4 inhibitor, AMD3100, or transfection of siRNA targeting CXCR4. OV6(+) HCC cells may represent a subpopulation of T-ICs with augmented invasion and metastasis potential, which contribute to progression and metastasis of HCC. The SDF-1/CXCR4 axis also provides therapeutic targets for elimination of liver T-ICs.Journal of Hepatology 05/2012; 57(3):613-20. DOI:10.1016/j.jhep.2012.04.024 · 10.40 Impact Factor
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ABSTRACT: The concept of cancer stem cells (CSCs) proposes that solely CSCs are capable of generating tumor metastases. However, how CSCs maintain their invasion and migration abilities, the most important properties of metastatic cells, still remains elusive. Here we used CD133 to mark a specific population from human ovarian cancer cell line and ovarian cancer tissue and determined its hyperactivity in migration and invasion. Therefore, we labeled this population as cancer stem-like cells (CSLCs). In comparison to CD133(-) non-CSLCs, chemokine CCL5 and its receptors, CCR1, CCR3, and CCR5, were consistently upregulated in CSLCs, and most importantly, blocking of CCL5, CCR1, or CCR3 effectively inhibits the invasive capacity of CSLCs. Mechanistically, we identified that this enhanced invasiveness is mediated through nuclear factor κB (NF-κB) activation and the consequently elevated MMP9 secretion. Our results suggested that the autocrine activation of CCR1 and CCR3 by CCL5 represents one of major mechanisms underlying the metastatic property of ovarian CSLCs. STEM CELLS2012;30:2309-2319.Stem Cells 10/2012; 30(10):2309-19. DOI:10.1002/stem.1194 · 7.70 Impact Factor