Localization patterns of cathepsins K and X and their predictive value in glioblastoma

  • Barbara Breznik National Institute of Biology
  • Clara Limback
  • Andrej Porčnik
  • Andrej Blejec
  • Miha Koprivnikar Krajnc
  • Roman Bošnjak
  • Janko Kos
  • Cornelis J.F. van Noorden
  • Tamara T. Lah

Abstract

BACKGROUND: Glioblastoma is a highly aggressive central nervous system neoplasm characterized by extensive infiltration of malignant cells into parenchyma, thus preventing complete tumor eradication. Cysteine cathepsins B, S, L and K are involved in cancer progression and are overexpressed in glioblastoma. We report here for the first time that cathepsin X mRNA and protein are also abundantly present in malignant glioma.

METHODS: Gene expression of cathepsins K and X was analyzed using publically-available transcriptomic datasets and correlated to glioma grade and glioblastoma subtype. Kaplan-Maier survival analysis was performed to evaluate the predictive value of cathepsins K and X mRNA expression. Cathepsin protein expression was localized and semi-quantified in tumor tissues by immunohistochemistry.

RESULTS: Highest gene expression of cathepsins K and X was found in glioblastoma, in particular in the mesenchymal subtype. Overall, high mRNA expression of cathepsin X, but not that of cathepsin K, correlated with poor patients’ survival. Cathepsins K and X proteins were abundantly and heterogeneously expressed in glioblastoma tissue. Immuno-labeling of cathepsins K and X was observed in areas of CD133-positive glioblastoma stem cells, localized around arterioles in their niches that also expressed SDF-1α and CD68. mRNA levels of both cathepsins K and X correlated with mRNA levels of markers of glioblastoma stem cells and their niches.

CONCLUSIONS: The presence of both cathepsins in glioblastoma stem cell niche regions indicates their possible role in regulation of glioblastoma stem cell homing in their niches. The clinical relevance of this data needs to be elaborated in further prospective studies.

Author Biography

Barbara Breznik, National Institute of Biology
Department of Genetic Toxicology and Cancer Biology
Published
2018-12-17
How to Cite
Breznik, B., Limback, C., Porčnik, A., Blejec, A., Koprivnikar Krajnc, M., Bošnjak, R., Kos, J., J.F. van Noorden, C., & T. Lah, T. (2018). Localization patterns of cathepsins K and X and their predictive value in glioblastoma. Radiology and Oncology, 52(4). Retrieved from https://radioloncol.com/index.php/ro/article/view/3078
Section
Experimental oncology