Li Yue, Zhao Long, Huo Yunlong, Yang Xianghong, Li Yong, Xu Hao, Li Xiao-Feng
Department of Nuclear Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
The First Affiliated Hospital, Jinan University, Guangzhou, China.
Front Oncol. 2022 Dec 22;12:1019360. doi: 10.3389/fonc.2022.1019360. eCollection 2022.
Tumor hypoxia is frequently observed in primary solid malignancies, but the hypoxic status of tumor cells floating in body cavity effusions is largely unknown, especially in patients. This study was to observe the hypoxia and proliferation status of cancer cells floating in effusions in mice and patients.
The distribution of hypoxia in cancer cells floating in ascites was first studied in nude mice. Hypoxia was detected by immunofluorescent visualization of pimonidazole and GLUT-1. For cancer patients, we retrospectively collected 21 ascites and 7 pleural effusion sample blocks of cancer patients, which were confirmed to contain tumor cells. Immunohistochemistry was performed to detect the expression of endogenous hypoxic markers HIF-1α and GLUT-1, proliferation index Ki-67. F-FDG PET/CT was performed to detect the glucose metabolism status of tumor cells in effusions.
The tumor cells collected from ascites were positive for pimonidazole and GLUT-1, which suggesting that the cancer cells floating in ascites were hypoxic. Patterns of tumor hypoxia in human patients are similar to those observed in animal. HIF-1α and GLUT-1 were expressed by tumor cells in nearly all 28 cytological cases. For Ki-67 index, ascites tumor cells had a relatively low expression level compared with their corresponding primary or its metastatic lesions. Tumor cells in effusions showed high F-FDG uptake indicated the enhanced activity of glucose metabolism.
Tumor cells in body cavity effusions, as a unique subgroup of tumor, are in a state of hypoxia and low proliferation, which would be one of the driven causes of chemo-radiotherapy resistance. Novel therapeutic interventions are urgently needed to overcome tumor hypoxia.
原发性实体恶性肿瘤中常可见肿瘤缺氧，但体腔积液中漂浮的肿瘤细胞的缺氧状态在很大程度上尚不清楚，尤其是在患者中。本研究旨在观察小鼠和患者体腔积液中漂浮的癌细胞的缺氧和增殖状态。
首先在裸鼠中研究腹水漂浮癌细胞中的缺氧分布。通过匹莫硝唑和葡萄糖转运蛋白1（GLUT-1）的免疫荧光可视化检测缺氧情况。对于癌症患者，我们回顾性收集了21例癌症患者的腹水样本块和7例胸腔积液样本块，这些样本均证实含有肿瘤细胞。进行免疫组织化学检测内源性缺氧标志物缺氧诱导因子-1α（HIF-1α）和GLUT-1的表达以及增殖指数Ki-67。进行氟代脱氧葡萄糖正电子发射断层显像/X线计算机体层成像（F-FDG PET/CT）检测积液中肿瘤细胞的葡萄糖代谢状态。
从腹水中收集的肿瘤细胞匹莫硝唑和GLUT-1呈阳性，这表明腹水中漂浮的癌细胞处于缺氧状态。人类患者的肿瘤缺氧模式与在动物中观察到的相似。在几乎所有28例细胞学病例中，肿瘤细胞均表达HIF-1α和GLUT-1。对于Ki-67指数，腹水肿瘤细胞与其相应的原发性肿瘤或转移灶相比表达水平相对较低。积液中的肿瘤细胞显示出高F-FDG摄取，表明葡萄糖代谢活性增强。
体腔积液中的肿瘤细胞作为肿瘤的一个独特亚群，处于缺氧和低增殖状态，这可能是放化疗耐药的驱动原因之一。迫切需要新的治疗干预措施来克服肿瘤缺氧。
