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Similarities Between Stem Cell Niches in Glioblastoma and Bone Marrow: Rays of Hope for Novel Treatment Strategies.
Journal of Histochemistry & Cytochemistry ( IF 1.9 ) Pub Date : 2019-09-30 , DOI: 10.1369/0022155419878416
Vashendriya V V Hira 1, 2 , Barbara Breznik 1 , Miloš Vittori 3 , Annique Loncq de Jong 2 , Jernej Mlakar 4 , Roelof-Jan Oostra 5 , Mohammed Khurshed 2, 6 , Remco J Molenaar 1, 2, 6 , Tamara Lah 1 , Cornelis J F Van Noorden 1, 2
Affiliation  

Glioblastoma is the most aggressive primary brain tumor. Slowly dividing and therapy-resistant glioblastoma stem cells (GSCs) reside in protective peri-arteriolar niches and are held responsible for glioblastoma recurrence. Recently, we showed similarities between GSC niches and hematopoietic stem cell (HSC) niches in bone marrow. Acute myeloid leukemia (AML) cells hijack HSC niches and are transformed into therapy-resistant leukemic stem cells (LSCs). Current clinical trials are focussed on removal of LSCs out of HSC niches to differentiate and to become sensitized to chemotherapy. In the present study, we elaborated further on these similarities by immunohistochemical analyses of 17 biomarkers in paraffin sections of human glioblastoma and human bone marrow. We found all 17 biomarkers to be expressed both in hypoxic peri-arteriolar HSC niches in bone marrow and hypoxic peri-arteriolar GSC niches in glioblastoma. Our findings implicate that GSC niches are being formed in glioblastoma as a copy of HSC niches in bone marrow. These similarities between HSC niches and GSC niches provide a theoretic basis for the development of novel strategies to force GSCs out of their niches, in a similar manner as in AML, to induce GSC differentiation and proliferation to render them more sensitive to anti-glioblastoma therapies.

中文翻译:

胶质母细胞瘤和骨髓中干细胞壁ches之间的相似性:新型治疗策略的希望之光。

胶质母细胞瘤是最具侵略性的原发性脑肿瘤。缓慢分裂且具有治疗抗性的胶质母细胞瘤干细胞(GSC)驻留在小动脉周围的保护性壁and中,并负责胶质母细胞瘤的复发。最近,我们显示了GSC壁ni与骨髓中造血干细胞(HSC)壁ches之间的相似性。急性骨髓性白血病(AML)细胞劫持了HSC壁ni,并转化为对治疗有抵抗力的白血病干细胞(LSC)。当前的临床试验集中于从HSC壁removal中去除LSC,以区分并变得对化学疗法敏感。在本研究中,我们通过对人胶质母细胞瘤和人骨髓石蜡切片中的17种生物标记物的免疫组织化学分析,进一步阐述了这些相似性。我们发现所有17种生物标志物均在骨髓缺氧的小动脉周围HSC壁和成胶质细胞瘤的缺氧的小动脉周围GSC壁中表达。我们的发现暗示胶质母细胞瘤中形成了GSC壁as,作为骨髓中HSC壁ches的副本。HSC壁ches和GSC壁ches之间的相似之处为开发新策略以与AML中类似的方式迫使GSC脱离其壁ches提供理论基础,从而诱导GSC分化和增殖,从而使其对抗胶质母细胞瘤疗法更加敏感。
更新日期:2019-12-25
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