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01.12.2018 | Primary research | Ausgabe 1/2018 Open Access

Cancer Cell International 1/2018

Membrane expression of thymidine kinase 1 and potential clinical relevance in lung, breast, and colorectal malignancies

Zeitschrift:
Cancer Cell International > Ausgabe 1/2018
Autoren:
Evita G. Weagel, Weston Burrup, Roman Kovtun, Edwin J. Velazquez, Abigail M. Felsted, Michelle H. Townsend, Zachary E. Ence, Erica Suh, Stephen R. Piccolo, K. Scott Weber, Richard A. Robison, Kim L. O’Neill
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12935-018-0633-9) contains supplementary material, which is available to authorized users.
A correction to this article is available online at https://​doi.​org/​10.​1186/​s12935-019-0749-6.

Abstract

Background

Lung, breast, and colorectal malignancies are the leading cause of cancer-related deaths in the world causing over 2.8 million cancer-related deaths yearly. Despite efforts to improve prevention methods, early detection, and treatments, survival rates for advanced stage lung, breast, and colon cancer remain low, indicating a critical need to identify cancer-specific biomarkers for early detection and treatment. Thymidine kinase 1 (TK1) is a nucleotide salvage pathway enzyme involved in cellular proliferation and considered an important tumor proliferation biomarker in the serum. In this study, we further characterized TK1’s potential as a tumor biomarker and immunotherapeutic target and clinical relevance.

Methods

We assessed TK1 surface localization by flow cytometry and confocal microscopy in lung (NCI-H460, A549), breast (MDA-MB-231, MCF7), and colorectal (HT-29, SW620) cancer cell lines. We also isolated cell surface proteins from HT-29 cells and performed a western blot confirming the presence of TK1 on cell membrane protein fractions. To evaluate TK1’s clinical relevance, we compared TK1 expression levels in normal and malignant tissue through flow cytometry and immunohistochemistry. We also analyzed RNA-Seq data from The Cancer Genome Atlas (TCGA) to assess differential expression of the TK1 gene in lung, breast, and colorectal cancer patients.

Results

We found significant expression of TK1 on the surface of NCI-H460, A549, MDA-MB-231, MCF7, and HT-29 cell lines and a strong association between TK1’s localization with the membrane through confocal microscopy and Western blot. We found negligible TK1 surface expression in normal healthy tissue and significantly higher TK1 expression in malignant tissues. Patient data from TCGA revealed that the TK1 gene expression is upregulated in cancer patients compared to normal healthy patients.

Conclusions

Our results show that TK1 localizes on the surface of lung, breast, and colorectal cell lines and is upregulated in malignant tissues and patients compared to healthy tissues and patients. We conclude that TK1 is a potential clinical biomarker for the treatment of lung, breast, and colorectal cancer.
Zusatzmaterial
Additional file 1. Flow cytometry histograms of cell lines treated with anti-TK1 antibodies. Cells treated with anti-TK1 antibodies (black line) showed a shift in fluorescence compared to isotype controls (gray area).
Literatur
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