Colamaio Marianna, Tosti Nadia, Puca Francesca, Mari Alessia, Gattordo Rosaria, Kuzay Yalçın, Federico Antonella, Pepe Anna, Sarnataro Daniela, Ragozzino Elvira, Raia Maddalena, Hirata Hidenari, Gemei Marica, Mimori Koshi, Del Vecchio Luigi, Battista Sabrina, Fusco Alfredo
a Istituto di Endocrinologia ed Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.
b Molecular Pathology Unit, Institute of Pathology , University Hospital Basel , Basel , Switzerland.
Expert Opin Ther Targets. 2016 Oct;20(10):1169-79. doi: 10.1080/14728222.2016.1220543. Epub 2016 Sep 8.
Glioblastoma multiforme (GBM) develops from a small subpopulation of stem-like cells, which are endowed with the ability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. These cells are resistant to conventional chemo- and radiotherapy and are hence also responsible for tumor recurrence. HMGA1 overexpression has been shown to correlate with proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of cancer stem cells from colon cancer. The role of HMGA1 in GBM tumor stem cells is not completely understood.
We have investigated the role of HMGA1 in brain tumor stem cell (BTSC) self-renewal, stemness and resistance to temozolomide by shRNA- mediated HMGA1 silencing.
We first report that HMGA1 is overexpressed in a subset of BTSC lines from human GBMs. Then, we show that HMGA1 knockdown reduces self-renewal, sphere forming efficiency and stemness, and sensitizes BTSCs to temozolomide. Interestingly, HMGA1 silencing also leads to reduced tumor initiation ability in vivo.
These results demonstrate a pivotal role of HMGA1 in cancer stem cell gliomagenesis and endorse HMGA1 as a suitable target for CSC-specific GBM therapy.
多形性胶质母细胞瘤（GBM）由一小部分干细胞样细胞发展而来，这些细胞具有自我更新、增殖的能力，并能产生多个神经上皮谱系的后代。这些细胞对传统的化疗和放疗具有抗性，因此也是肿瘤复发的原因。HMGA1的过表达已被证明与GBM的增殖、侵袭和血管生成相关，并影响结肠癌癌症干细胞的自我更新。HMGA1在GBM肿瘤干细胞中的作用尚未完全了解。
我们通过shRNA介导的HMGA1沉默研究了HMGA1在脑肿瘤干细胞（BTSC）自我更新、干性及对替莫唑胺抗性中的作用。
我们首次报道HMGA1在来自人类GBM的一部分BTSC系中过表达。然后，我们表明HMGA1敲低会降低自我更新、成球效率和干性，并使BTSC对替莫唑胺敏感。有趣的是，HMGA1沉默还会导致体内肿瘤起始能力降低。
这些结果证明了HMGA1在癌症干细胞胶质瘤发生中的关键作用，并支持将HMGA1作为CSC特异性GBM治疗的合适靶点。
