Centre de Recherche en Cancérologie de Lyon - Université Claude Bernard Lyon 1, UMR CNRS 5286, INSERM 1052, Centre Léon Bérard, 69373, Lyon, France.
Institut Curie, Paris Sciences et Lettres (PSL) Research University, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 144, Paris, France.
J Exp Clin Cancer Res. 2022 Nov 16;41(1):324. doi: 10.1186/s13046-022-02514-y.
Aerotaxis, the chemotactism to oxygen, is well documented in prokaryotes. We previously reported for the first time that non-tumorigenic breast epithelial cells also display unequivocal directional migration towards oxygen. This process is independent of the hypoxia-inducible factor (HIF)/prolyl hydroxylase domain (PHD) pathway but controlled by the redox regulation of epidermal growth factor receptor (EGFR), with a reactive oxygen species (ROS) gradient overlapping the oxygen gradient at low oxygen concentration. Since hypoxia is an acknowledged hallmark of cancers, we addressed the putative contribution of aerotaxis to cancer metastasis by studying the directed migration of cancer cells from an hypoxic environment towards nearby oxygen sources, modelling the in vivo migration of cancer cells towards blood capillaries.
We subjected to the aerotactic test described in our previous papers cells isolated from fresh breast tumours analysed by the Pathology Department of the Saint-Etienne University Hospital (France) over a year. The main selection criterion, aside from patient consent, was the size of the tumour, which had to be large enough to perform the aerotactic tests without compromising routine diagnostic tests. Finally, we compared the aerotactic properties of these primary cells with those of commonly available breast cancer cell lines.
We show that cells freshly isolated from sixteen human breast tumour biopsies, representative of various histological characteristics and grades, are endowed with strong aerotactic properties similar to normal mammary epithelial cell lines. Strikingly, aerotaxis of these primary cancerous cells is also strongly dependent on both EGFR activation and ROS. In addition, we demonstrate that aerotaxis can trigger directional invasion of tumour cells within the extracellular matrix contrary to normal mammary epithelial cells. This contrasts with results obtained with breast cancer cell lines, in which aerotactic properties were either retained or impaired, and in some cases, even lost during the establishment of these cell lines.
Altogether, our results support that aerotaxis may play an important role in breast tumour metastasis. In view of these findings, we discuss the prospects for combating metastatic spread.
IRBN1462021/CHUSTE.
趋氧性，即对氧气的化学趋向性，在原核生物中已有充分的记录。我们之前首次报道，非致瘤性乳腺上皮细胞也表现出明确的朝向氧气的定向迁移。这个过程不依赖于缺氧诱导因子（HIF）/脯氨酰羟化酶结构域（PHD）途径，而是由表皮生长因子受体（EGFR）的氧化还原调控控制，在低氧浓度下，活性氧（ROS）梯度与氧气梯度重叠。由于缺氧是癌症公认的标志之一，我们通过研究来自低氧环境的癌细胞向附近氧气源的定向迁移，模拟癌细胞向血管毛细血管的体内迁移，来研究趋氧性对癌症转移的潜在贡献。
我们对一年来法国圣艾蒂安大学医院病理学系分离的新鲜乳腺癌肿瘤细胞进行了我们之前论文中描述的趋氧性测试。除了患者同意外，主要的选择标准是肿瘤的大小，必须足够大，以便在不影响常规诊断测试的情况下进行趋氧性测试。最后，我们比较了这些原代细胞与常用的乳腺癌细胞系的趋氧特性。
我们表明，从十六个人类乳腺癌活检组织中分离的新鲜细胞，代表了各种组织学特征和分级，具有类似于正常乳腺上皮细胞系的强烈趋氧特性。引人注目的是，这些原发性癌细胞的趋氧性也强烈依赖于 EGFR 的激活和 ROS。此外，我们证明趋氧性可以触发肿瘤细胞在细胞外基质中的定向侵袭，而正常乳腺上皮细胞则不会。这与乳腺癌细胞系的结果形成对比，在这些细胞系中，趋氧特性要么保留，要么受损，在某些情况下，甚至在建立这些细胞系的过程中丢失。
总的来说，我们的结果支持趋氧性可能在乳腺癌转移中发挥重要作用。鉴于这些发现，我们讨论了对抗转移扩散的前景。
IRBN1462021/CHUSTE。
