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Expression of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma cells is downregulated upon inhibition of BRAF

  • Authors:
    • Karolina Uranowska
    • Tanja Kalic
    • Veronika Valtsanidis
    • Melitta Kitzwögerer
    • Heimo Breiteneder
    • Christine Hafner
  • View Affiliations / Copyright

    Affiliations: Department of Dermatology, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, 3100 St. Poelten, Austria, Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria, Department of Pathology, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, 3100 St. Poelten, Austria
    Copyright: © Uranowska et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 14
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    Published online on: February 2, 2021
       https://doi.org/10.3892/or.2021.7965
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Abstract

Chondroitin sulfate proteoglycan 4 (CSPG4) is a multifunctional transmembrane proteoglycan involved in spreading, migration and invasion of melanoma. In addition to the activating BRAF V600E mutation, CSPG4 was shown to promote MAPK signaling by mediating the growth‑factor induced activation of receptor tyrosine kinases. However, it remains elusive which factors regulate CSPG4 expression. Therefore, the aim of the present study was to examine whether BRAF and MEK inhibitors have an effect on the expression of CSPG4. We exposed a panel of BRAF‑mutant CSPG4‑positive or ‑negative melanoma cell lines to BRAF and MEK inhibitors. Protein levels of CSPG4 were analyzed by flow cytometry (FACS), immunofluorescence microscopy (IF), and western blotting. CSPG4 mRNA levels were determined by quantitative PCR (qPCR). The prolonged exposure of cells to BRAF and MEK inhibitors resulted in markedly reduced levels of the CSPG4 protein in permanent resistant melanoma cells as well as decreased levels of its mRNA. We did not observe increasing levels of CSPG4 shedding into the culture supernatants. In addition, patient‑derived matched tumor samples following therapy with kinase inhibitors showed decreased numbers of CSPG4‑positive cells as compared to pre‑therapy tumor samples. Our results indicate that BRAF and MEK inhibition downregulates CSPG4 expression until the cells have developed permanent resistance. Our findings provide the basis for further investigation of the role of CSPG4 in the development of drug‑resistance in melanoma cells.
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Copy and paste a formatted citation
Spandidos Publications style
Uranowska K, Kalic T, Valtsanidis V, Kitzwögerer M, Breiteneder H and Hafner C: Expression of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma cells is downregulated upon inhibition of BRAF. Oncol Rep 45: 14, 2021.
APA
Uranowska, K., Kalic, T., Valtsanidis, V., Kitzwögerer, M., Breiteneder, H., & Hafner, C. (2021). Expression of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma cells is downregulated upon inhibition of BRAF. Oncology Reports, 45, 14. https://doi.org/10.3892/or.2021.7965
MLA
Uranowska, K., Kalic, T., Valtsanidis, V., Kitzwögerer, M., Breiteneder, H., Hafner, C."Expression of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma cells is downregulated upon inhibition of BRAF". Oncology Reports 45.4 (2021): 14.
Chicago
Uranowska, K., Kalic, T., Valtsanidis, V., Kitzwögerer, M., Breiteneder, H., Hafner, C."Expression of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma cells is downregulated upon inhibition of BRAF". Oncology Reports 45, no. 4 (2021): 14. https://doi.org/10.3892/or.2021.7965
Copy and paste a formatted citation
x
Spandidos Publications style
Uranowska K, Kalic T, Valtsanidis V, Kitzwögerer M, Breiteneder H and Hafner C: Expression of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma cells is downregulated upon inhibition of BRAF. Oncol Rep 45: 14, 2021.
APA
Uranowska, K., Kalic, T., Valtsanidis, V., Kitzwögerer, M., Breiteneder, H., & Hafner, C. (2021). Expression of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma cells is downregulated upon inhibition of BRAF. Oncology Reports, 45, 14. https://doi.org/10.3892/or.2021.7965
MLA
Uranowska, K., Kalic, T., Valtsanidis, V., Kitzwögerer, M., Breiteneder, H., Hafner, C."Expression of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma cells is downregulated upon inhibition of BRAF". Oncology Reports 45.4 (2021): 14.
Chicago
Uranowska, K., Kalic, T., Valtsanidis, V., Kitzwögerer, M., Breiteneder, H., Hafner, C."Expression of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma cells is downregulated upon inhibition of BRAF". Oncology Reports 45, no. 4 (2021): 14. https://doi.org/10.3892/or.2021.7965
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