Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas

Murase, Masaki; Kano, Masanobu; Tsukahara, Tomohide; Takahashi, Akiko; Torigoe, Toshihiko; Kawaguchi, Satoshi; Kimura, Shigeharu; Wada, Takuro; Uchihashi, Yoshito; Kondo, Toru; Yamashita, Toshihiko; Sato, Noriyuki

doi:10.1038/sj.bjc.6605330

Cited by 119 publications

(117 citation statements)

References 51 publications

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“…DNAJB8 protein expression was detected in postmeiotic sperm and spermatid. Previous studies have shown that DNAJB6, DNAJB1, and DNAJB13 are also expressed in the testis (30)(31)(32), and Dnaja1 was reported to (34)(35)(36). SP cells derived from RCC and normal renal tubule epithelia have also been reported (37,38); however, the tumor-initiating ability of those RCC SP cells has not been characterized yet.…”

Section: Discussionmentioning

confidence: 99%

HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells

et al. 2012

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Cancer stem-like cells (CSC) are a small population of cancer cells with superior tumor initiating, self-renewal, and differentiation properties. In this study, we show that the cancer-testis antigen and HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma (RCC). DNAJB8 overexpression increased the percentage of side population (SP) cells representing CSCs in RCC cells, enhancing their tumor-initiating ability. Conversely, attenuation of DNAJB8 decreased SP cells and reduced tumor-initiating ability. The utility of DNAJB8 as an immunologic target was established in DNA vaccination experiments. Compared with immunization with the tumor-associated antigen survivin, which was expressed in both CSCs and non-CSCs in RCC, immunization with Dnajb8 expression plasmids yielded stronger antitumor effects. Together, our findings suggest that DNAJB8 plays a role in CSC maintenance and that it offers a candidate for CSC-targeting immunotherapy in RCC.

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Section: Discussionmentioning

confidence: 99%

HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells

et al. 2012

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“…[4][5][6][7]13 Their enhanced capacity to form sarcospheres is a surrogate of their self-renewal property regardless of the method used to characterize and isolate this cell subpopulation from Targeting tumor-initiating cells in osteosarcoma N Rainusso et al the tumor bulk. Sarcospheres have previously been shown to be resistant to doxorubicin, cisplatin and vincristine, 8,9 and we now show they are also resistant to methotrexate.…”

Section: Discussionmentioning

confidence: 99%

“…3 TICs have been identified in OS by the expression of certain surface markers or as a 'side population' through the exclusion of the vital dye Hoechst 33342. [4][5][6] In addition, OS TICs can be grown in culture as sphere-like structures (sarcospheres) under serum starvation, 7 a property that allows functional testing of different anti-neoplastic agents against this tumor cell compartment. Furthermore, OS TICs have been reported to be resistant to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy targeting HER2 with genetically modified T cells eliminates tumor-initiating cells in osteosarcoma

et al. 2011

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Despite radical surgery and multi-agent chemotherapy, less than one third of patients with recurrent or metastatic osteosarcoma (OS) survive. The limited efficacy of current therapeutic approaches to target tumor-initiating cells (TICs) may explain this dismal outcome. The purpose of this study was to assess the impact of modified T cells expressing a human epidermal growth factor receptor (HER2)-specific chimeric antigen receptor in the OS TIC compartment of human established cell lines. Using the sarcosphere formation assay, we found that OS TICs were resistant to increasing methotrexate concentrations. In contrast, HER2-specific T cells decreased markedly sarcosphere formation capacity and the ability to generate bone tumors in immunodeficient mice after orthotopic transplantation. In vivo, administration of HER2-specific T cells significantly reduced TICs in bulky tumors as judged by decreased sarcosphere forming efficiency in OS cells isolated from explanted tumors. We demonstrate that HER2-specific T cells target drug resistant TICs in established OS cell lines, suggesting that incorporating immunotherapy into current treatment strategies for OS has the potential to improve outcomes.

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“…5 CSCs/CICs were successfully isolated as SP cells in several types of cancers. [6][7][8][9] The second method is cell surface markers. CD44 þ CD24 À/low for breast CSCs/CICs 3 and CD133 for glioma CSCs/CICs 10 and several other cell surface markers were reported for isolation of a CSC/CIC population.…”

mentioning

confidence: 99%

SOX2 is overexpressed in stem-like cells of human lung adenocarcinoma and augments the tumorigenicity

Nakatsugawa

Takahashi

Hirohashi

et al. 2011

Laboratory Investigation

112

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Recently, the SOX2 gene has been reported to be amplified in human lung squamous cell carcinomas. However, its roles in human lung adenocarcinomas are still elusive. In this study, we analyzed the functions of SOX2 in cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) derived from human lung adenocarcinoma. Human lung CSCs/CICs were isolated as higher tumorigenic side population (SP) cells using Hoechst 33342 dye from several lung cancer cell lines. Four of nine lung cancer cell lines were positive for SP cells (LHK2, 1-87, A549, Lc817). The ratios of SP cells ranged from 0.4% for Lc817 to 2.8% for LHK2. To analyze the molecular aspects of SP cells, we performed microarray screening and RT-PCR analysis, and isolated SOX2 as one of a SP cell-specific gene. SOX2 was expressed predominantly in LHK2 and 1-87 SP cells, and was also expressed in several other cancer cell lines. The expression of SOX2 protein in primary human lung cancer tissues were also confirmed by immunohistochemical staining, and SOX2 was detected in more than 80% of primary lung cancer tissues. To address SOX2 molecular functions, we established a SOX2-overexpressed LHK2 and A549 cell line (LHK2-SOX2 and A549-SOX2). LHK2-SOX2 cells showed higher rates of SP cells and higher expression of POU5F1 compared with control cells. LHK2-SOX2 and A549-SOX2 cells showed relatively higher tumorigenicity than control cells. On the other hand, SOX2 mRNA knockdown of LHK2 SP cells by gene-specific siRNA completely abrogated tumorigenicity in vivo. These observations indicate that SOX2 has a role in maintenance of stemness and tumorigenicity of human lung adenocarcinoma CSCs/CICs and is a potential target for treatment.

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Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas

Cited by 119 publications

References 51 publications

HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells

HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem–like Cells

Immunotherapy targeting HER2 with genetically modified T cells eliminates tumor-initiating cells in osteosarcoma

SOX2 is overexpressed in stem-like cells of human lung adenocarcinoma and augments the tumorigenicity

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