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Proteoglycans as potential microenvironmental biomarkers for colon cancer

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Abstract

Glycosylation changes occur widely in colon tumours, suggesting glycosylated molecules as potential biomarkers for colon cancer diagnostics. In this study, proteoglycans (PGs) expression levels and their transcriptional patterns are investigated in human colon tumours in vivo and carcinoma cells in vitro. According to RT-PCR analysis, normal and cancer colon tissues expressed a specific set of PGs (syndecan-1, perlecan, decorin, biglycan, versican, NG2/CSPG4, serglycin, lumican, CD44), while the expression of glypican-1, brevican and aggrecan was almost undetectable. Overall transcriptional activity of the PGs in normal and cancer tissues was similar, although expression patterns were different. Expression of decorin and perlecan was down-regulated 2-fold in colon tumours, while biglycan and versican expression was significantly up-regulated (6-fold and 3-fold, respectively). Expression of collagen1A1 was also increased 6-fold in colon tumours. However, conventional HCT-116 colon carcinoma and AG2 colon cancer-initiating cells did not express biglycan and decorin and were versican-positive and -negative, respectively, demonstrating an extracellular origin of the PGs in cancer tissue. Selective expression of heparan sulfate (HS) proteoglycans syndecan-1 and perlecan in the AG2 colon cancer-initiating cell line suggests these PGs as potential biomarkers for cancer stem cells. Overall transcriptional activity of the HS biosynthetic system was similar in normal and cancer tissues, although significant up-regulation of extracellular sulfatases SULF1/2 argues for a possible distortion of HS sulfation patterns in colon tumours. Taken together, the obtained results suggest versican, biglycan, collagen1A1 and SULF1/2 expression as potential microenvironmental biomarkers and/or targets for colon cancer diagnostics and treatment.

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Acknowledgments

The work was supported by a research grant from the Russian Foundation for Basic Research (RFBR 12-04-01657a) and the Ministry of Education and Science of the Russian Federation.

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The authors declare that they have no competing interests or financial disclosure.

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Authors and Affiliations

  1. Institute of Molecular Biology and Biophysics SB RAMS, Timakova str 2, Novosibirsk, 630117, Russia

    Anastasia V. Suhovskih & Elvira V. Grigorieva

  2. Novosibirsk State University, Novosibirsk, Russia

    Anastasia V. Suhovskih & Elvira V. Grigorieva

  3. Novosibirsk State Medical University, Novosibirsk, Russia

    Svetlana V. Aidagulova

  4. Institute of Molecular Biology and Genetics, UNAS, Kiev, Ukraine

    Vladimir I. Kashuba

  5. MTC, Karolinska Institute, Stockholm, Sweden

    Vladimir I. Kashuba & Elvira V. Grigorieva

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  1. Anastasia V. Suhovskih
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  2. Svetlana V. Aidagulova
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  3. Vladimir I. Kashuba
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  4. Elvira V. Grigorieva
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Correspondence to Elvira V. Grigorieva.

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Suhovskih, A.V., Aidagulova, S.V., Kashuba, V.I. et al. Proteoglycans as potential microenvironmental biomarkers for colon cancer. Cell Tissue Res 361, 833–844 (2015). https://doi.org/10.1007/s00441-015-2141-8

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  • DOI: https://doi.org/10.1007/s00441-015-2141-8

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