胶质母细胞瘤和骨髓干细胞间的相似性:新型治疗策略的希望之光

Vashendriya V. V. Hira, Barbara Breznik, Annique Loncq de Jong, M. Khurshed, Remco J. Molenaar, Tamara Lah, Cornelis van Noorden
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引用次数: 1

摘要

胶质母细胞瘤是最具侵袭性的原发性脑肿瘤。胶质母细胞瘤干细胞(GSCs)分裂缓慢且对治疗具有抵抗力,它们驻留在动脉周围的保护性壁龛中,是GSC维持和胶质母细胞瘤复发的罪魁祸首。最近,我们发现GSC壁龛与骨髓中的造血干细胞(HSC)壁龛有相似之处。急性髓性白血病(AML)细胞劫持造血干细胞龛,并转化为分裂缓慢、耐药的白血病干细胞(LSCs)。目前临床试验的重点是将干细胞移出造血干细胞龛,使其分化并对化疗敏感。在本研究中,我们通过对人类胶质母细胞瘤和人类健康骨髓石蜡切片中的17种生物标志物进行免疫组化分析和荧光显微镜检查,进一步阐述了这些相似性。我们发现所有17种生物标志物在骨髓中缺氧的动脉周围造血干细胞龛和胶质母细胞瘤中缺氧的动脉周围造血干细胞龛中都有表达。我们的研究结果表明,胶质母细胞瘤中形成的造血干细胞龛是骨髓中造血干细胞龛的翻版。造血干细胞龛和成胶质细胞龛之间的这些相似之处为开发新的策略提供了理论基础,这些策略可以迫使成胶质细胞离开它们的龛,就像在急性髓细胞白血病中一样,诱导成胶质细胞分化和增殖,使它们对抗胶质母细胞瘤疗法更加敏感。
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Similarities Between Stem Cell Niches in Glioblastoma and Bone Marrow: Rays of Hope for Novel Treatment Strategies
Glioblastomais 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 GSC maintenance and 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 slowly‐dividing and 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 and fluorescence microscopy of17 biomarkers in paraffin sections of human glioblastoma and human healthy 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.
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