Juhász Péter, Méhes Gábor
Department of Pathology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
Int J Mol Sci. 2025 May 6;26(9):4423. doi: 10.3390/ijms26094423.
Intratumoral hypoxia is common in any form of malignancy initializing focal necrosis or tumor cell adaptation. Hypoxia inducible factor-1-driven reprogramming favors the loss of tumor cell proliferation (quiescence) and partial cellular reversion, induces stemness and/or mesenchymal-like features in the exposed tumor areas. The characteristic hypoxia-driven tumor cell phenotype is principally directed to reduce energy consumption and to enhance survival, but the gained features also contribute to growth advantage and induce the reorganization of the microenvironment and protective mechanisms against external stress. The hypoxia-induced phenotypic changes are at least in part reflected by conventional morphology in breast carcinoma. Intratumoral variability of classical morphological signs, such as the growth pattern, the histological grade, cell proliferation, necrosis, microcalcification, angiogenesis, and the immune cell infiltration is also related with the co-existence of hypoxic areas. Thus, a deeper understanding of hypoxia-activated mechanisms is required. The current paper aims to summarize the major tissue factors involved in the response to hypoxia and their potential contribution to the breast carcinoma phenotype.
肿瘤内缺氧在任何引发局灶性坏死或肿瘤细胞适应的恶性肿瘤形式中都很常见。缺氧诱导因子-1驱动的重编程有利于肿瘤细胞增殖丧失（静止）和部分细胞逆转，在暴露的肿瘤区域诱导干性和/或间充质样特征。典型的缺氧驱动的肿瘤细胞表型主要旨在减少能量消耗并提高存活率，但获得的特征也有助于生长优势，并诱导微环境的重组和针对外部应激的保护机制。缺氧诱导的表型变化至少部分反映在乳腺癌的传统形态学中。经典形态学特征的肿瘤内变异性，如生长模式、组织学分级、细胞增殖、坏死、微钙化、血管生成和免疫细胞浸润，也与缺氧区域的共存有关。因此，需要更深入地了解缺氧激活机制。本文旨在总结参与缺氧反应的主要组织因子及其对乳腺癌表型的潜在贡献。
