Enhanced capture system for mesenchymal‑type circulating tumor cells using a polymeric microfluidic device &lsquo;CTC‑Chip&rsquo; incorporating cell‑surface vimentin

Kanayama,Masatoshi; Yoneda,Kazue; Kuwata,Taiji; Mori,Masataka; Manabe,Takehiko; Oyama,Rintaro; Matsumiya,Hiroki; Takenaka,Masaru; Kuroda,Koji; Ohnaga,Takashi; Tanaka,Fumihiro

doi:10.3892/or.2024.8815

Enhanced capture system for mesenchymal‑type circulating tumor cells using a polymeric microfluidic device ‘CTC‑Chip’ incorporating cell‑surface vimentin

Authors:
- Masatoshi Kanayama
- Kazue Yoneda
- Taiji Kuwata
- Masataka Mori
- Takehiko Manabe
- Rintaro Oyama
- Hiroki Matsumiya
- Masaru Takenaka
- Koji Kuroda
- Takashi Ohnaga
- Fumihiro Tanaka
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Affiliations: Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu 807‑8555, Japan
Published online on: September 30, 2024 https://doi.org/10.3892/or.2024.8815
Article Number: 156

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Abstract

CellSearch, the only approved epithelial cell adhesion molecule (EpCAM)‑dependent capture system approved for clinical use, overlooks circulating tumor cells (CTCs) undergoing epithelial‑mesenchymal transition (EMT‑CTCs), which is considered a crucial subtype responsible for metastasis. To address this limitation, a novel polymeric microfluidic device ‘CTC‑chip’ designed for the easy introduction of any antibody was developed, enabling EpCAM‑independent capture. In this study, antibodies against EpCAM and cell surface vimentin (CSV), identified as cancer‑specific EMT markers, were conjugated onto the chip (EpCAM‑chip and CSV‑chip, respectively), and the capture efficiency was examined using lung cancer (PC9, H441 and A549) and colon cancer (DLD1) cell lines, classified into three types based on EMT markers: Epithelial (PC9), intermediate (H441 and DLD1) and mesenchymal (A549). PC9, H441 and DLD1 cells were effectively captured using the EpCAM‑chip (average capture efficiencies: 99.4, 88.8 and 90.8%, respectively) when spiked into blood. However, A549 cells were scarcely captured (13.4%), indicating that EpCAM‑dependent capture is not suitable for mesenchymal‑type cells. The expression of CSV tended to be higher in cells exhibiting mesenchymal properties and A549 cells were effectively captured with the CSV‑chip (72.4 and 88.4% at concentrations of 10 and 100 µg/ml, respectively) when spiked into PBS. When spiked into blood, the average capture efficiencies were 27.7 and 46.8% at concentrations of 10 and 100 µg/ml, respectively. These results suggest that the CSV‑chip is useful for detecting mesenchymal‑type cells and has potential applications in capturing EMT‑CTCs.

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1	Lozar T, Gersak K, Cemazar M, Kuhar CG and Jesenko T: The biology and clinical potential of circulating tumor cells. Radiol Oncol. 53:131–147. 2019. View Article : Google Scholar : PubMed/NCBI
2	Deng Z, Wu S, Wang Y and Shi D: Circulating tumor cell isolation for cancer diagnosis and prognosis. EBioMedicine. 83:1042372022. View Article : Google Scholar : PubMed/NCBI
3	Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW and Terstappen LW: Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 10:6897–6904. 2004. View Article : Google Scholar : PubMed/NCBI
4	Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Picus J, Morse M, Mitchell E, Miller MC, et al: Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 26:3213–3221. 2008. View Article : Google Scholar : PubMed/NCBI
5	Tanaka F, Yoneda K, Kondo N, Hashimoto M, Takuwa T, Matsumoto S, Okumura Y, Rahman S, Tsubota N, Tsujimura T, et al: Circulating tumor cell as a diagnostic marker in primary lung cancer. Clin Cancer Res. 15:6980–6986. 2009. View Article : Google Scholar : PubMed/NCBI
6	Brabletz S, Schuhwerk H, Brabletz T and Stemmler MP: Dynamic EMT: A multi-tool for tumor progression. EMBO J. 40:e1086472021. View Article : Google Scholar : PubMed/NCBI
7	Lu G, Lu Z, Li C, Huang X and Luo Q: Prognostic and therapeutic significance of circulating tumor cell phenotype detection based on epithelial-mesenchymal transition markers in early and midstage colorectal cancer first-line chemotherapy. Comput Math Methods Med. 2021:22945622021. View Article : Google Scholar : PubMed/NCBI
8	Gao Y, Fan WH, Song Z, Lou H and Kang X: Comparison of circulating tumor cell (CTC) detection rates with epithelial cell adhesion molecule (EpCAM) and cell surface vimentin (CSV) antibodies in different solid tumors: A retrospective study. PeerJ. 9:e107772021. View Article : Google Scholar : PubMed/NCBI
9	Ohnaga T, Shimada Y, Moriyama M, Kishi H, Obata T, Takata K, Okumura T, Nagata T, Muraguchi A and Tsukada K: Polymeric microfluidic devices exhibiting sufficient capture of cancer cell line for isolation of circulating tumor cells. Biomed Microdevices. 15:611–616. 2013. View Article : Google Scholar : PubMed/NCBI
10	Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, et al: Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 450:1235–1239. 2007. View Article : Google Scholar : PubMed/NCBI
11	Chikaishi Y, Yoneda K, Ohnaga T and Tanaka F: EpCAM-independent capture of circulating tumor cells with a ‘universal CTC-chip’. Oncol Rep. 37:77–82. 2017. View Article : Google Scholar : PubMed/NCBI
12	Kuwata T, Yoneda K, Mori M, Kanayama M, Kuroda K, Kaneko MK, Kato Y and Tanaka F: Detection of circulating tumor cells (CTCs) in malignant pleural mesothelioma (MPM) with the ‘universal’ CTC-chip and an anti-podoplanin antibody NZ-1.2. Cells. 9:8882020. View Article : Google Scholar : PubMed/NCBI
13	Kanayama M, Oyama R, Mori M, Taira A, Shinohara S, Kuwata T, Takenaka M, Yoneda K, Kuroda K, Ohnaga T, et al: Novel circulating tumor cell-detection chip combining conventional podoplanin and EGFR antibodies for all histological malignant pleural mesothelioma. Oncol Lett. 22:5222021. View Article : Google Scholar : PubMed/NCBI
14	Yoneda K, Kuwata T, Chikaishi Y, Mori M, Kanayama M, Takenaka M, Oka S, Hirai A, Imanishi N, Kuroda K, et al: Detection of circulating tumor cells with a novel microfluidic system in malignant pleural mesothelioma. Cancer Sci. 110:726–733. 2019. View Article : Google Scholar : PubMed/NCBI
15	Kanayama M, Kuwata T, Mori M, Nemoto Y, Nishizawa N, Oyama R, Matsumiya H, Taira A, Shinohara S, Takenaka M, et al: Prognostic impact of circulating tumor cells detected with the microfluidic ‘universal CTC-chip’ for primary lung cancer. Cancer Sci. 113:1028–1037. 2022. View Article : Google Scholar : PubMed/NCBI
16	Satelli A, Mitra A, Brownlee Z, Xia X, Bellister S, Overman MJ, Kopetz S, Ellis LM, Meng QH and Li S: Epithelial-mesenchymal transitioned circulating tumor cells capture for detecting tumor progression. Clin Cancer Res. 21:899–906. 2015. View Article : Google Scholar : PubMed/NCBI
17	Satelli A, Batth I, Brownlee Z, Mitra A, Zhou S, Noh H, Rojas CR, Li H, Meng QH and Li S: EMT circulating tumor cells detected by cell-surface vimentin are associated with prostate cancer progression. Oncotarget. 8:49329–49337. 2017. View Article : Google Scholar : PubMed/NCBI
18	Wei T, Zhang X, Zhang Q, Yang J, Chen Q, Wang J, Li X, Chen J, Ma T, Li G, et al: Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer. Cancer Lett. 452:237–243. 2019. View Article : Google Scholar : PubMed/NCBI
19	Li H, Zhu YZ, Xu L, Han T, Luan J, Li X, Liu Y, Wang Z, Liu Q, Kong X, et al: Exploring new frontiers: Cell surface vimentin as an emerging marker for circulating tumor cells and a promising therapeutic target in advanced gastric cancer. J Exp Clin Cancer Res. 43:1292024. View Article : Google Scholar : PubMed/NCBI
20	Riegger J and Brenner RE: Increase of cell surface vimentin is associated with vimentin network disruption and subsequent stress-induced premature senescence in human chondrocytes. Elife. 12:e914532023. View Article : Google Scholar : PubMed/NCBI
21	Markou A, Tzanikou E and Lianidou E: The potential of liquid biopsy in the management of cancer patients. Semin Cancer Biol. 84:69–79. 2022. View Article : Google Scholar : PubMed/NCBI
22	Alix-Panabières C, Marchetti D and Lang JE: Liquid biopsy: From concept to clinical application. Sci Rep. 13:216852023. View Article : Google Scholar : PubMed/NCBI
23	Strouhalova K, Přechová M, Gandalovičová A, Brábek J, Gregor M and Rosel D: Vimentin intermediate filaments as potential target for cancer treatment. Cancers (Basel). 12:1842020. View Article : Google Scholar : PubMed/NCBI
24	Usman S, Waseem NH, Nguyen TKN, Mohsin S, Jamal A, Teh MT and Waseem A: Vimentin is at the heart of epithelial mesenchymal transition (EMT) mediated metastasis. Cancers (Basel). 13:49852021. View Article : Google Scholar : PubMed/NCBI
25	Paulin D, Lilienbaum A, Kardjian S, Agbulut O and Li Z: Vimentin: Regulation and pathogenesis. Biochimie. 197:96–112. 2022. View Article : Google Scholar : PubMed/NCBI
26	Ramos I, Stamatakis K, Oeste CL and Pérez-Sala D: Vimentin as a multifaceted player and potential therapeutic target in viral infections. Int J Mol Sci. 21:46752020. View Article : Google Scholar : PubMed/NCBI
27	Xie X, Wang L, Wang X, Fan WH, Qin Y, Lin X, Xie Z, Liu M, Ouyang M, Li S and Zhou C: Evaluation of cell surface vimentin positive circulating tumor cells as a diagnostic biomarker for lung cancer. Front Oncol. 11:6726872021. View Article : Google Scholar : PubMed/NCBI
28	Yu J, Yang M, Peng T, Liu Y and Cao Y: Evaluation of cell surface vimentin positive circulating tumor cells as a prognostic biomarker for stage III/IV colorectal cancer. Sci Rep. 13:187912023. View Article : Google Scholar : PubMed/NCBI
29	Batth IS, Dao L, Satelli A, Mitra A, Yi S, Noh H, Li H, Brownlee Z, Zhou S, Bond J, et al: Cell surface vimentin-positive circulating tumor cell-based relapse prediction in a long-term longitudinal study of postremission neuroblastoma patients. Int J Cancer. 147:3550–3559. 2020. View Article : Google Scholar : PubMed/NCBI
30	Noh H, Zhao Q, Yan J, Kong LY, Gabrusiewicz K, Hong S, Xia X, Heimberger AB and Li S: Cell surface vimentin-targeted monoclonal antibody 86C increases sensitivity to temozolomide in glioma stem cells. Cancer Lett. 433:176–185. 2018. View Article : Google Scholar : PubMed/NCBI
31	Batth IS and Li S: Discovery of cell-surface vimentin (CSV) as a sarcoma target and development of CSV-targeted IL12 immune therapy. Adv Exp Med Biol. 1257:169–178. 2020. View Article : Google Scholar : PubMed/NCBI