Heterogeneity of MiR-10b Expression in Circulating Tumor Cells

Overview

Journal Sci Rep

Specialty Science

Date 2015 Nov 3

PMID 26522916

Citations 17

Authors

Christin Gasch

Prue N Plummer

Lidija Jovanovic

Linda M McInnes

David Wescott

Christobel M Saunders

Andreas Schneeweiss

Markus Wallwiener

Colleen Nelson

Kevin J Spring

Sabine Riethdorf

Erik W Thompson

Klaus Pantel

Albert S Mellick

Affiliations

Soon will be listed here.

Abstract

Circulating tumor cells (CTCs) in the blood of cancer patients are recognized as important potential targets for future anticancer therapies. As mediators of metastatic spread, CTCs are also promising to be used as 'liquid biopsy' to aid clinical decision-making. Recent work has revealed potentially important genotypic and phenotypic heterogeneity within CTC populations, even within the same patient. MicroRNAs (miRNAs) are key regulators of gene expression and have emerged as potentially important diagnostic markers and targets for anti-cancer therapy. Here, we describe a robust in situ hybridization (ISH) protocol, incorporating the CellSearch(®) CTC detection system, enabling clinical investigation of important miRNAs, such as miR-10b on a cell by cell basis. We also use this method to demonstrate heterogeneity of such as miR-10b on a cell-by-cell basis. We also use this method to demonstrate heterogeneity of miR-10b in individual CTCs from breast, prostate and colorectal cancer patients.

Citing Articles

miR-455-3p has superior diagnostic potential to PSA in peripheral blood for prostate cancer.

Cen Y, Feng S, Xu Y, Zhang C, Lin X, Ye X PLoS One. 2025; 20(2):e0317385.

PMID: 39951446 PMC: 11828392. DOI: 10.1371/journal.pone.0317385.

Lessons (to be) learned from liquid biopsies: assessment of circulating cells and cell-free DNA in cancer and pregnancy-acquired microchimerism.

Bergmann L, Afflerbach A, Yuan T, Pantel K, Smit D Semin Immunopathol. 2025; 47(1):14.

PMID: 39893314 PMC: 11787191. DOI: 10.1007/s00281-025-01042-z.

Circulating Tumor Cells: How Far Have We Come with Mining These Seeds of Metastasis?.

Radhakrishnan V, Kaifi J, Suvilesh K Cancers (Basel). 2024; 16(4).

PMID: 38398206 PMC: 10887304. DOI: 10.3390/cancers16040816.

Circulating miR-10b, soluble urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 as predictors of non-small cell lung cancer progression and treatment response.

Setiawan L, Setiabudy R, Kresno S, Sutandyo N, Syahruddin E, Jovianti F Cancer Biomark. 2023; 39(2):137-153.

PMID: 38073374 PMC: 11002724. DOI: 10.3233/CBM-220222.

Clinical Applications of Liquid Biopsy in Colorectal Cancer Screening: Current Challenges and Future Perspectives.

Galos D, Gorzo A, Balacescu O, Sur D Cells. 2022; 11(21).

PMID: 36359889 PMC: 9657568. DOI: 10.3390/cells11213493.

References

Scher H, Jia X, de Bono J, Fleisher M, Pienta K, Raghavan D . Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol. 2009; 10(3):233-9. PMC: 2774131. DOI: 10.1016/S1470-2045(08)70340-1. View

Park S, Gaur A, Lengyel E, Peter M . The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008; 22(7):894-907. PMC: 2279201. DOI: 10.1101/gad.1640608. View

Swennenhuis J, Tibbe A, Levink R, Sipkema R, Terstappen L . Characterization of circulating tumor cells by fluorescence in situ hybridization. Cytometry A. 2009; 75(6):520-7. DOI: 10.1002/cyto.a.20718. View

Sasayama T, Nishihara M, Kondoh T, Hosoda K, Kohmura E . MicroRNA-10b is overexpressed in malignant glioma and associated with tumor invasive factors, uPAR and RhoC. Int J Cancer. 2009; 125(6):1407-13. DOI: 10.1002/ijc.24522. View

Trang P, Weidhaas J, Slack F . MicroRNAs as potential cancer therapeutics. Oncogene. 2009; 27 Suppl 2:S52-7. PMC: 10033140. DOI: 10.1038/onc.2009.353. View

Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson E . Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol. 2010; 28(4):341-7. PMC: 2852471. DOI: 10.1038/nbt.1618. View

Riethdorf S, Muller V, Zhang L, Rau T, Loibl S, Komor M . Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res. 2010; 16(9):2634-45. DOI: 10.1158/1078-0432.CCR-09-2042. View

Jorgensen S, Baker A, Moller S, Nielsen B . Robust one-day in situ hybridization protocol for detection of microRNAs in paraffin samples using LNA probes. Methods. 2010; 52(4):375-81. DOI: 10.1016/j.ymeth.2010.07.002. View

Farazi T, Spitzer J, Morozov P, Tuschl T . miRNAs in human cancer. J Pathol. 2010; 223(2):102-15. PMC: 3069496. DOI: 10.1002/path.2806. View

10.

Roth C, Rack B, Muller V, Janni W, Pantel K, Schwarzenbach H . Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res. 2010; 12(6):R90. PMC: 3046429. DOI: 10.1186/bcr2766. View

11.

Roth C, Kasimir-Bauer S, Pantel K, Schwarzenbach H . Screening for circulating nucleic acids and caspase activity in the peripheral blood as potential diagnostic tools in lung cancer. Mol Oncol. 2011; 5(3):281-91. PMC: 5528292. DOI: 10.1016/j.molonc.2011.02.002. View

12.

Sieuwerts A, Mostert B, Vries J, Peeters D, de Jongh F, Stouthard J . mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients. Clin Cancer Res. 2011; 17(11):3600-18. DOI: 10.1158/1078-0432.CCR-11-0255. View

13.

Fendler A, Jung M, Stephan C, Honey R, Stewart R, Pace K . miRNAs can predict prostate cancer biochemical relapse and are involved in tumor progression. Int J Oncol. 2011; 39(5):1183-92. DOI: 10.3892/ijo.2011.1128. View

14.

Van Raamsdonk C, Tilghman S . Optimizing the detection of nascent transcripts by RNA fluorescence in situ hybridization. Nucleic Acids Res. 2001; 29(8):E42-2. PMC: 31326. DOI: 10.1093/nar/29.8.e42. View

15.

Allard W, Matera J, Miller M, Repollet M, Connelly M, Rao C . Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004; 10(20):6897-904. DOI: 10.1158/1078-0432.CCR-04-0378. View

16.

Speel E, Herbergs J, Ramaekers F, Hopman A . Combined immunocytochemistry and fluorescence in situ hybridization for simultaneous tricolor detection of cell cycle, genomic, and phenotypic parameters of tumor cells. J Histochem Cytochem. 1994; 42(7):961-6. DOI: 10.1177/42.7.8014480. View

17.

Kubota K, Ohashi A, Imachi H, Harada H . Improved in situ hybridization efficiency with locked-nucleic-acid-incorporated DNA probes. Appl Environ Microbiol. 2006; 72(8):5311-7. PMC: 1538721. DOI: 10.1128/AEM.03039-05. View

18.

Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C, Rack B . Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin Cancer Res. 2007; 13(3):920-8. DOI: 10.1158/1078-0432.CCR-06-1695. View

19.

Thompson R, Deo M, Turner D . Analysis of microRNA expression by in situ hybridization with RNA oligonucleotide probes. Methods. 2007; 43(2):153-61. PMC: 2101764. DOI: 10.1016/j.ymeth.2007.04.008. View

20.

Nakata K, Ohuchida K, Mizumoto K, Kayashima T, Ikenaga N, Sakai H . MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis. Surgery. 2011; 150(5):916-22. DOI: 10.1016/j.surg.2011.06.017. View