Wilhelm Christian, Scherzad Agmal, Bregenzer Maximilian, Meyer Till, Gehrke Thomas, Kleinsasser Norbert, Hagen Rudolf, Hackenberg Stephan
Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Julius Maximilian University of Wuerzburg, D-97080 Wuerzburg, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, Kepler University, A-4020 Linz, Austria.
Oncol Lett. 2020 Nov;20(5):229. doi: 10.3892/ol.2020.12092. Epub 2020 Sep 11.
Mesenchymal stem cells (MSCs) exhibit strong tropism towards tumor tissue. While MSCs generally surround tumors, they can also infiltrate tumors and thereby influence their proliferation. Interactions between MSCs and tumor cells are usually tested under normoxia, but the majority of solid tumors, including head and neck squamous cell carcinoma (HNSCC), are also characterized by hypoxic areas. Hence, the present study aimed to assess the interaction between MSCs and tumor cells under hypoxic conditions. MSCs were cultivated under normoxia and hypoxia, and conditioned media were used to cultivate the HNSCC cell line FaDu. The cell cycle distribution and viability of MSCs and the proliferation of FaDu cells were analyzed under normoxia and hypoxia, and changes in cytokine levels in the conditioned media were evaluated. No cell cycle changes were observed for MSCs after 24 h of cultivation under hypoxia, but the cell viability had declined. Hypoxia also led to a decrease in the proliferation of FaDu cells; however, FaDu cells proliferated faster after 48 h under hypoxia compared with normoxic conditions. This effect was reversed after incubation under normoxia for 72 h and hypoxia for 72 h. While these changes constituted a trend, these differences were not statistically significant. A cytokine assay showed an increase in interleukin (IL)-6 in the hypoxic medium. Overall, the results indicated that there was an interaction between MSCs and tumor cells. The presence or absence of oxygen seemed to influence the functionality of MSCs and their protumorigenic properties, in which IL-6 was identified as a potential mediator. Since MSCs are a component of the tumor stroma, further and studies are needed to investigate this interaction in order to develop novel approaches for tumor therapy.
间充质干细胞（MSCs）对肿瘤组织表现出强烈的趋向性。虽然MSCs通常环绕肿瘤，但它们也可浸润肿瘤并由此影响其增殖。MSCs与肿瘤细胞之间的相互作用通常在常氧条件下进行检测，但包括头颈部鳞状细胞癌（HNSCC）在内的大多数实体瘤也具有缺氧区域的特征。因此，本研究旨在评估缺氧条件下MSCs与肿瘤细胞之间的相互作用。将MSCs在常氧和缺氧条件下培养，并用条件培养基培养HNSCC细胞系FaDu。在常氧和缺氧条件下分析MSCs的细胞周期分布和活力以及FaDu细胞的增殖情况，并评估条件培养基中细胞因子水平的变化。在缺氧条件下培养24小时后，未观察到MSCs的细胞周期变化，但细胞活力有所下降。缺氧还导致FaDu细胞的增殖减少；然而，与常氧条件相比，FaDu细胞在缺氧条件下48小时后增殖更快。在常氧条件下培养72小时和在缺氧条件下培养72小时后，这种效应被逆转。虽然这些变化构成了一种趋势，但这些差异无统计学意义。细胞因子检测显示缺氧培养基中白细胞介素（IL）-6增加。总体而言，结果表明MSCs与肿瘤细胞之间存在相互作用。氧的存在与否似乎影响MSCs的功能及其促肿瘤特性，其中IL-6被确定为一种潜在的介质。由于MSCs是肿瘤基质的一个组成部分，需要进一步的研究来调查这种相互作用，以便开发新的肿瘤治疗方法。
