Rausch Linda K, Netzer Nikolaus C, Hoegel Josef, Pramsohler Stephan
Hermann Buhl Institute for Hypoxia and Sleep Medicine Research, Bad Aibling, Germany.
Department of Sports Science, University Innsbruck, Innsbruck, Austria.
Front Oncol. 2017 Sep 25;7:211. doi: 10.3389/fonc.2017.00211. eCollection 2017.
The development of breast cancer cells is linked to hypoxia. The hypoxia-induced factor HIF-1α influences metastasis through neovascularization. Hypoxia seems to decrease the responsiveness to hormonal treatment due to loss of estrogen receptors (ERs). Obesity is discussed to increase hypoxia in adipocytes, which promotes a favorable environment for tumor cells in mammary fat tissue, whereas, tumor cells profit from good oxygen supply and are influenced by its deprivation as target regions within tumors show. This review gives an overview of the current state on research of hypoxia and breast cancer in human adipose tissue.
A systematic literature search was conducted on PubMed (2000-2016) by applying hypoxia and/or adipocytes and breast cancer as keywords. Review articles were excluded as well as languages other than English or German. There was no restriction regarding the study design or type of breast cancer. A total of 35 papers were found. Eight studies were excluded due to missing at least two of the three keywords. One paper was removed due to Russian language, and one was dismissed due to lack of adherence. Seven papers were identified as reviews. After applying exclusion criteria, 18 articles were eligible for inclusion.
Two articles describe the impairment of mammary epithelial cell polarization through hypoxic preconditioning. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF-1α which causes the loss of ER α protein as stated in four articles. Four articles analyzed that increased activation of HIF's induces a series of transcriptions resulting in tumor angiogenesis. HIF inhibition, especially when combined with cytotoxic chemotherapy, holds strong potential for tumor suppression as stated in further four articles. In two articles there is evidence of a strong connection between hypoxia, oxidative stress and a poor prognosis for breast cancer via HIF regulated pathways. Acute hypoxia seems to normalize the microenvironment in breast cancer tissue and has proven to affect tumor growth positively as covered in two articles.
This review indicates that the development of breast cancer is influenced by hypoxia. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF-1α.
乳腺癌细胞的发展与缺氧有关。缺氧诱导因子HIF-1α通过新血管生成影响转移。由于雌激素受体（ERs）的丧失，缺氧似乎会降低对激素治疗的反应性。有观点认为肥胖会增加脂肪细胞中的缺氧情况，这为乳腺脂肪组织中的肿瘤细胞营造了有利环境，然而，肿瘤细胞受益于良好的氧气供应，并且如肿瘤内的靶区域所示，它们也会受到缺氧的影响。本综述概述了人类脂肪组织中缺氧与乳腺癌的研究现状。
在PubMed（2000 - 2016年）上进行系统的文献检索，使用缺氧和/或脂肪细胞以及乳腺癌作为关键词。排除综述文章以及英语或德语以外语言的文章。对研究设计或乳腺癌类型没有限制。共找到35篇论文。由于至少缺少三个关键词中的两个，排除了8项研究。因语言为俄语排除1篇论文，因缺乏依从性排除1篇论文。7篇论文被确定为综述。应用排除标准后，18篇文章符合纳入条件。
两篇文章描述了缺氧预处理对乳腺上皮细胞极化的损害。如四篇文章所述，大量脂肪细胞由于HIF-1α表达增加而促进癌症进展，HIF-1α表达增加会导致ERα蛋白丢失。四篇文章分析，HIF的激活增加会诱导一系列转录，从而导致肿瘤血管生成。如另外四篇文章所述，抑制HIF，尤其是与细胞毒性化疗联合使用时，具有很强的肿瘤抑制潜力。两篇文章中有证据表明，通过HIF调节的途径，缺氧、氧化应激与乳腺癌预后不良之间存在密切联系。两篇文章提到，急性缺氧似乎使乳腺癌组织中的微环境正常化，并已证明对肿瘤生长有积极影响。
本综述表明，乳腺癌的发展受缺氧影响。大量脂肪细胞由于HIF-1α表达增加而促进癌症进展。
