Cancer Stem Cells and Their Mechanism of Chemo-Radiation Resistance

Kim, Yonghyun; Joo, Kyeung Min; Jin, Juyoun; Nam, Do‐Hyun

doi:10.15283/ijsc.2009.2.2.109

Cited by 77 publications

(54 citation statements)

References 40 publications

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“…22,24,25 The role of Wnt pathway has been shown in colon and breast cancers, 26,27 and a recent study in breast cancer have reported that radiation enriches stem cell-like breast progenitor cells with highly activated Wnt signaling. 28 Wnt pathways in GBM have been investigated by a few groups including ours; however, the role of Wnt in GBM has remained largely hypothetical.…”

Section: Discussionmentioning

confidence: 99%

Wnt activation is implicated in glioblastoma radioresistance

Kim

Lee

et al. 2012

Laboratory Investigation

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Glioblastoma (GBM) patients have dismal median survival even with the most rigorous treatments currently available. Radiotherapy is the most effective non-surgical therapy for GBM patients; however, patients succumb due to tumor recurrence within a year. To develop a curative therapeutic approach, we need to better understand the underlying molecular mechanism of radiation resistance in GBM. Towards this goal, we developed an in vivo orthotopic GBM model system that mimics the radiation response of human GBM, using both established-GBM cell line and patient-derived freshly dissociated GBM specimen. In-vivo ionizing radiation (IR) treatment prolonged the survival of mice with intracranical tumor derived from U373MG, but failed to prevent tumor recurrence. U373MG and GBM578 cells isolated after in-vivo IR (U373-IR and 578-IR) were more clonogenic and enriched with stem cell-like characteristics, compared with mock-treated control tumor cells. Transcriptomic analyses and quantitative real-time reverse-transcription PCR analyses using these matched GBM cells before and after radiation treatment revealed that Wnt pathways were preferentially activated in post-IR GBM cells. U373-IR cells and 578-IR were enriched with cells positive for both active b-catenin (ABC) and Sox2 population, and this subpopulation was further increased after additional in-vitro radiation treatment, suggesting that radiation resistance of GBM is mediated due, in part, to the activation of stem cell-associated pathways including Wnt. Finally, pharmacological and siRNA inhibition of Wnt pathway significantly decreased the survival and clonogenicity of GBM cells and reduced their ABC þ /Sox2 þ population. Together, these data suggest that Wnt activation is a molecular mechanism to confer GBM radioresistance and an important therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Wnt activation is implicated in glioblastoma radioresistance

Kim

Lee

et al. 2012

Laboratory Investigation

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139

105

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“…CSCs are a specialized subset of tumor cells with stem cell-like properties, such as self-renewal and differentiation potential (collectively, ''stemness''). [1][2][3] CSCs are hypothesized to be at the apex of the tumor cell hierarchy and are the only subset of cells capable of initiating tumors that comprise CSCs and non-stem bulk tumor cells. The exact origin of CSCs is unclear.…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8][9] Functionally, they have also been shown to have heightened chemo-and radio-resistance and thus explain the tumor relapse observed in many patients. 1,2 Because of these characteristics, CSCs are postulated to promote the epithelialto-mesenchymal transition (EMT) during cancer metastasis. [10][11][12] CSCs are thus positioned as the main barrier against cancer cures but also a hope in the search for them.…”

Section: Introductionmentioning

confidence: 99%

The Role of Biomaterials on Cancer Stem Cell Enrichment and Behavior

Ordikhani

Kim

Zustiak

2015

JOM

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The theory of cancer stem cells (CSCs) and their role in cancer metastasis, tumorigenicity and resistance to therapy is slowly shifting the emphasis on the search for cancer cure: more evidence is surfacing that a successful therapy should be geared against this rare cancer cell population. Unfortunately, CSCs are difficult to culture in vitro which severely limits the progress of CSC research. This review gives a brief overview of CSCs and their microenvironment, with particular focus on studies that used in vitro biomaterial-based models and biomaterial/CSC interfaces for the enrichment of CSCs. Biomaterial properties relevant to CSC behaviors are also addressed. While the discussed research field is still in its infancy, it appears that in vitro cancer models that include a biomaterial can support CSC enrichment and this has proved indispensable to the study of their biology as well as the development of novel cancer therapies.

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“…However, one of the challenges of molecular-targeting drugs is that multiple agent-resistant cancer stem cells can remain difficult to eradicate. 8 By contrast, in our experience, immunotherapy targeting AURKA appeared to have the potential to eradicate cancer stem cells. We have previously identified the immunogenic epitope derived from AURKA, which could induce leukemia-cidal CTLs.…”

mentioning

confidence: 70%