Hypoxia, low, non-physiological oxygen tension is a key regulator of tumor microenvironment, determining the pathological tumor vascularization. Alleviation of hypoxia through vessel normalization may be a promising therapeutic approach. We aimed to assess the role of low oxygen tension in PTEN-related pathways and proangiogenic response, in vitro, in two different tumor cell lines, focusing on potential therapeutic targets for tumor vessel normalization. Downregulation of PTEN in hypoxia mediates the activation of distinct mechanisms: cytoplasmic pAKT activation in melanoma and pMDM2 modulation in kidney cancer. We show that hypoxia-induced proangiogenic potential was stronger in Renca cells than B16 F10-confirmed by a distinct secretory potential and different ability to affect endothelial cells functions. Therefore, the impact of hypoxia on PTEN-mediated regulation may determine the therapeutic targets and effectiveness of vessel normalization and intrinsic characteristics of cancer cell have to be taken into account when designing treatment.

中文翻译：

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对两种不同肿瘤细胞模型中缺氧影响的比较分析表明，PTEN 对促血管生成途径的控制存在差异。

缺氧、低、非生理性氧张力是肿瘤微环境的关键调节因子，决定肿瘤的病理血管化。通过血管正常化缓解缺氧可能是一种有前途的治疗方法。我们的目的是在体外评估两种不同肿瘤细胞系中低氧张力在 PTEN 相关通路和促血管生成反应中的作用，重点关注肿瘤血管正常化的潜在治疗靶点。缺氧时 PTEN 的下调介导不同机制的激活：黑色素瘤中的细胞质 p​​AKT 激活和肾癌中的 pMDM2 调节。我们表明，Renca 细胞中缺氧诱导的促血管生成潜力比 B16 F10 更强，这通过独特的分泌潜力和影响内皮细胞功能的不同能力得到证实。因此，缺氧对 PTEN 介导的调节的影响可能决定治疗靶点和血管正常化的有效性，并且在设计治疗时必须考虑癌细胞的内在特征。