Kulasinghe Arutha, Perry Chris, Warkiani Majid E, Blick Tony, Davies Anthony, O'Byrne Ken, Thompson Erik W, Nelson Colleen C, Vela Ian, Punyadeera Chamindie
The School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia.
Translational Research Institute, Woolloongabba, QLD, Australia.
Oncotarget. 2016 Sep 13;7(37):60101-60109. doi: 10.18632/oncotarget.11159.
Minimally invasive techniques are required for the identification of head and neck cancer (HNC) patients who are at an increased risk of metastasis, or are not responding to therapy. An approach utilised in other solid cancers is the identification and enumeration of circulating tumour cells (CTCs) in the peripheral blood of patients. Low numbers of CTCs has been a limiting factor in the HNC field to date. Here we present a methodology to expand HNC patient derived CTCs ex-vivo. As a proof of principle study, 25 advanced stage HNC patient bloods were enriched for circulating tumour cells through negative selection and cultured in 2D and 3D culture environments under hypoxic conditions (2% O2, 5% CO2). CTCs were detected in 14/25 (56%) of patients (ranging from 1-15 CTCs/5 mL blood). Short term CTC cultures were successfully generated in 7/25 advanced stage HNC patients (5/7 of these cultures were from HPV+ patients). Blood samples from which CTC culture was successful had higher CTC counts (p = 0.0002), and were predominantly from HPV+ patients (p = 0.007). This is, to our knowledge, the first pilot study to culture HNC CTCs ex-vivo. Further studies are warranted to determine the use of short term expansion in HNC and the role of HPV in promoting culture success.
对于那些转移风险增加或对治疗无反应的头颈癌（HNC）患者，需要采用微创技术进行识别。在其他实体癌中使用的一种方法是识别和计数患者外周血中的循环肿瘤细胞（CTC）。迄今为止，低数量的CTC一直是HNC领域的一个限制因素。在此，我们提出一种在体外扩增源自HNC患者的CTC的方法。作为一项原理验证研究，通过阴性选择对25例晚期HNC患者的血液进行循环肿瘤细胞富集，并在低氧条件（2% O2，5% CO2）下在二维和三维培养环境中进行培养。在14/25（56%）的患者中检测到了CTC（范围为1 - 15个CTC/5 mL血液）。在7/25例晚期HNC患者中成功建立了短期CTC培养物（其中5/7的培养物来自HPV阳性患者）。成功进行CTC培养的血样具有更高的CTC计数（p = 0.0002），并且主要来自HPV阳性患者（p = 0.007）。据我们所知，这是第一项在体外培养HNC CTC的初步研究。有必要进行进一步的研究，以确定短期扩增在HNC中的应用以及HPV在促进培养成功方面的作用。
