&lt;em&gt;In Vivo&lt;/em&gt; Model for Testing Effect of Hypoxia on Tumor Metastasis

Hong, Sung-Hyeok; Tilan, Jason U.; Galli, Susana; Acree, Rachel; Connors, Katherine; Mahajan, Akanksha; Wietlisbach, Larissa E; Polk, Taylor; Iżycka‐Świeszewska, Ewa; Lee, Yi-Chien; Cavalli, Luciane R.; Rodriguez, Olga; Albanese, Chris; Kitlińska, Joanna

doi:10.3791/54532-v

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“…Hypoxia in solid tumors is a major negative prognostic factor for tumor progression because decreased availability of oxygen in tumors increases treatment resistance and enhances tumor progression and metastasis (Hong et al, 2016;Joseph, Harishankar, Pillai, & Devi, 2018;Ren et al, 2013). Adaptation to hypoxia has been shown to increase tumor cell invasiveness and metastatic potential, contributing to radio-or chemotherapeutic resistance (Klein et al, 2017;Shen et al, 2017).…”

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confidence: 99%

Blocking OLFM4/HIF‐1α axis alleviates hypoxia‐induced invasion, epithelial–mesenchymal transition, and chemotherapy resistance in non‐small‐cell lung cancer

Gao

Wang

Zhao

et al. 2019

Journal Cellular Physiology

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Hypoxia is a common biological hallmark of solid cancers, which has been proposed to be associated with oncogenesis and chemotherapy resistance. The purpose of the present study was to investigate the role and underlying mechanisms of olfactomedin 4 (OLFM4) in the hypoxia‐induced invasion, epithelial–mesenchymal transition (EMT), and chemotherapy resistance of non‐small‐cell lung cancer (NSCLC). We observed dramatically upregulated expression of OLFM4 in several NSCLC cell lines, and this effect was more pronounced in A549 and H1299 cells. In addition, our data revealed that OLFM4 expression was remarkably increased in both A549 and H1299 cells under hypoxic microenvironment, accompanied by enhanced levels of hypoxia‐inducible factor (HIF)‐1α protein. The HIF‐1α level was elevated in response to hypoxia, resulting in the regulation of OLFM4. Interestingly, OLFM4 was a positive regulator of hypoxia‐driven HIF‐1α production. Moreover, depletion of OLFM4 modulated multiple EMT‐associated proteins, as evidenced by the enhanced E‐cadherin levels along with the diminished expression of N‐cadherin and vimentin in response to hypoxia, and thus blocked invasion ability of A549 and H1299 cells following exposure to hypoxia. Furthermore, ablation of OLFM4 accelerated the sensitivity of A549 cells to cisplatin under hypoxic conditions, implying that OLFM4 serves as a key regulator in chemotherapeutic resistance under hypoxia. In conclusion, OLFM4/HIF‐1α axis might be a potential therapeutic strategy for NSCLC.

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