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Hypoxia Increases Thyroid Cancer Stem Cell-Enriched Side Population.

ABSTRACT: INTRODUCTION:Hypoxic stress is a feature of rapidly growing thyroid tumours. Cancer progression is thought to be driven by a small population of tumour cells possessing stem cell properties. Hypoxia-inducible factors (HIFs) are important mediators of hypoxia. Both HIF-1alpha and HIF-2alpha have been reported to be expressed in thyroid cancers. There is growing evidence that the HIF pathway plays a significant role in the maintenance of thyroid cancer stem cells (CSC). METHODOLOGY:We have isolated thyroid CSC from a papillary thyroid cancer-derived cell line (BCPAP) and an anaplastic thyroid cancer-derived cell line (SW1736) as side population (SP) cells (a putative stem cell population) and treated them with cobalt chloride (II) to induce hypoxia. RESULTS AND DISCUSSION: We observed an increase in the SP of cells within the thyroid cancer cell lines following induction of hypoxia.

SUBMITTER: Mahkamova K

PROVIDER: S-EPMC5762807 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Hypoxia Increases Thyroid Cancer Stem Cell-Enriched Side Population.

Mahkamova K K Latar N N Aspinall S S Meeson A A

World journal of surgery 20180201 2

<h4>Introduction</h4>Hypoxic stress is a feature of rapidly growing thyroid tumours. Cancer progression is thought to be driven by a small population of tumour cells possessing stem cell properties. Hypoxia-inducible factors (HIFs) are important mediators of hypoxia. Both HIF-1alpha and HIF-2alpha have been reported to be expressed in thyroid cancers. There is growing evidence that the HIF pathway plays a significant role in the maintenance of thyroid cancer stem cells (CSC).<h4>Methodology</h4> ...[more]

PMID: 29167950

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Project description:BackgroundA major challenge in the treatment of pancreatic ductal adenocarcinoma is the failure of chemotherapy, which is likely due to the presence of the cancer stem cells (CSCs).ObjectiveTo identify side population (SP) cells and characterize s-like properties in human pancreatic cancer cell lines (h-PCCLs) and to exploit the efficacy of concomitant targeting of multiple key transcription factors governing the stemness of pancreatic CSCs in suppressing CSC-like phenotypes.MethodsFlow cytometry and Hoechst 33342 DNA-binding dye efflux assay were used to sort SP and non-SP (NSP) cells from three h-PCCLs: PANC-1, SW1990, and BxPc-3. The self-renewal ability, invasiveness, migration and drug resistance of SP cells were evaluated. Expression of CSC marker genes was analyzed. Tumorigenicity was assessed using a xenograft model in nude mice. Effects of a complex decoy oligonucleotide (cdODN-SCO) designed to simultaneously targeting Sox2, Oct4 and c-Myc were assessed.ResultsCSCs were enriched in the side proportion (SP) cells contained in the h-PCCLs and they possessed aggressive growth, invasion, migration and drug-resistance properties, compared with NSP cells. SP cells overexpressed stem cell markers CD133 and ALDH1, pluripotency maintaining factors Nanog, Sox2 and Oct4, oncogenic transcription factor c-Myc, signaling molecule Notch1, and drug resistant gene ABCG2. Moreover, SP cells consistently demonstrated significantly greater tumorigenicity than NSP cells in xenograft model of nude mice. CdODN-SOC efficiently suppressed all CSC properties and phenotypes, and minimized the tumorigenic capability of the SP cells and the resistance to chemotherapy. By comparison, the negative control failed to do so.ConclusionThe findings indicate that targeting the key genes conferring the stemness of CSCs can efficiently eliminate CSC-like phenotypes, and thus may be considered a new approach for cancer therapy. Specifically, the present study establishes the combination of Sox2/Oct4/c-Myc targeting as a potential anti-pancreatic cancer agent worthy of further studies in preclinical settings.

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Hypoxia Increases Thyroid Cancer Stem Cell-Enriched Side Population.

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Hypoxia Increases Thyroid Cancer Stem Cell-Enriched Side Population.

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