Effect of Concomitant Radiochemotherapy on Invasion Potential of Glioblastoma

Pathol Oncol Res. 2016 Jan;22(1):155-60. doi: 10.1007/s12253-015-9989-5. Epub 2015 Oct 9.

Abstract

Glioblastoma (GBM) is the most common primary brain tumor in adults with inevitable recurrence after oncotherapy. The insufficient effect of "gold standard" temozolomide-based concomitant radiochemotherapy may be due to the inability to prevent tumor cell invasion. Peritumoral infiltration depends mainly on the interaction between extracellular matrix (ECM) components and cell membrane receptors. Changes in invasive behaviour after oncotherapy can be evaluated at the molecular level by determining the RNA expression and protein levels of the invasion-related ECM components. The expression of nineteen ECM molecules was determined at both RNA and protein levels in thirty-one GBM samples. Fifteen GBM samples originated from the first surgical procedure on patients before oncotherapy, and sixteen GBM samples were collected at the second surgery due to local recurrence after concomitant chemoirradiation. RNA expressions were measured with qRT-PCR, and protein levels were determined by quantitative analysis of Western blots. Only MMP-9 RNA transcript level was reduced (p < 0.05) whereas at protein level, eight molecules showed changes concordant with RNA expression with significant decrease in brevican only. The results suggest that concomitant radiochemotherapy does not have sufficient impact on the expression of invasion-related ECM components of glioblastoma, oncotherapy does not significantly affect its invasive behavior. To avoid the spread of tumors into the brain parenchyma, supplementation of antiproliferative treatment with anti-invasive agents may be worth consideration in oncotherapy for glioblastoma.

Keywords: Extracellular matrix; Glioblastoma; Invasion; Radiochemotherapy; Temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / therapy*
  • Chemoradiotherapy*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Glioblastoma / therapy*
  • Humans
  • Mass Spectrometry
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • Extracellular Matrix Proteins
  • RNA, Messenger