Barazi Muhi Dean, Aboubechara John Paul, Sulman Muhammad, Maraqah Haitham H, Abu-Asab Mones S, Lee Han Sung, Aboud Orwa
School of Biosciences, Rice University, Houston, TX, USA.
Department of Neurology and Neurosurgery, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA.
Ultrastruct Pathol. 2025 Aug 24:1-9. doi: 10.1080/01913123.2025.2551738.
Extensive research has begun to uncover the molecular characteristics of high grade gliomas. However, an ultrastructural understanding of their pathogenesis remains largely unexplored. Multinucleated giant cells are large cells with multiple nuclei thought to form from the fusion of multiple neoplastic cells. In this study, we aim to elucidate the nature of the multinucleated giant cells (MGCs) within -wild type glioblastoma (GBM) and -mutant astrocytoma, grade 4, by characterizing their phenotypes, ontogenies, morphologies, prevalence, significance, and potential impact on tumor progression and treatment resistance. Utilizing transmission electron microscopy (TEM), we examined 30 tumors (18 -wild type GBMs and 12 -mutant astrocytomas) and found that they share two types of MGCs. Type 1 is formed by the fusion of several tumor cells. Type 2 seems to be produced by tumor fibrillar cells filled with intermediate filaments (IF) and lipids through two processes, either by cell fusion or by the immigration of naked nuclei to a larger IF-filled tumor cell. Our results showed that MGCs are abundantly present in 43% of cases, making them less rare than previously believed. The two MGC types occurred solely or in combination in both types of gliomas. Furthermore, MGCs appear non-proliferative; and therefore, their contribution to tumorigenesis and proliferation is not yet fully resolved.
广泛的研究已开始揭示高级别胶质瘤的分子特征。然而，对其发病机制的超微结构理解在很大程度上仍未得到探索。多核巨细胞是具有多个细胞核的大细胞，被认为是由多个肿瘤细胞融合形成的。在本研究中，我们旨在通过对野生型胶质母细胞瘤（GBM）和4级突变型星形细胞瘤中的多核巨细胞（MGCs）的表型、起源、形态、发生率、意义以及对肿瘤进展和治疗耐药性的潜在影响进行表征，来阐明其本质。利用透射电子显微镜（TEM），我们检查了30个肿瘤（18个野生型GBM和12个突变型星形细胞瘤），发现它们共有两种类型的MGCs。1型由几个肿瘤细胞融合形成。2型似乎是由充满中间丝（IF）和脂质的肿瘤纤维细胞通过两种过程产生的，要么通过细胞融合，要么通过裸核迁移到一个更大的充满IF的肿瘤细胞中。我们的结果表明，43%的病例中大量存在MGCs，这使得它们并不像之前认为的那么罕见。两种类型的胶质瘤中均单独或联合出现这两种MGCs类型。此外，MGCs似乎不具有增殖性；因此，它们对肿瘤发生和增殖的作用尚未完全明确。
