Novel cancer stem cell marker MVP enhances temozolomide-resistance in glioblastoma

Kum Hee Noh, Song Hee Lee, Haeri Lee, Ae Jin Jeong, Kyu Oh Kim, Hyun Mu Shin, Hang Rae Kim, Myung Jin Park, Jong Bae Park, Jiyoung Lee, Sang Kyu Ye

Research output: Contribution to journalArticlepeer-review

Abstract

The resistance of highly aggressive glioblastoma multiforme (GBM) to chemotherapy is a major clinical problem resulting in a poor prognosis. GBM contains a rare population of self-renewing cancer stem cells (CSCs) that proliferate, spurring the growth of new tumors, and evade chemotherapy. In cancer, major vault protein (MVP) is thought to contribute to drug resistance. However, the role of MVP as CSCs marker remains unknown and whether MVP could sensitize GBM cells to Temozolomide (TMZ) also is unclear. We found that sensitivity to TMZ was suppressed by significantly increasing the MVP expression in GBM cells with TMZ resistance. Also, MVP was associated with the expression of other multidrug-resistant proteins in tumorsphere of TMZ-resistant GBM cell, and was highly co-expressed with CSC markers in tumorsphere culture. On the other hands, knockdown of MVP resulted in reduced sphere formation and invasive capacity. Moreover, high expression of MVP was associated with tumor malignancy and survival rate in glioblastoma patients. Our study describes that MVP is a potentially novel maker for glioblastoma stem cells and may be useful as a target for preventing TMZ resistance in GBM patients.

Original languageEnglish
Article number101255
JournalTranslational Oncology
Volume15
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • Cancer stem cells
  • Glioblastoma
  • Major vault protein
  • Temozolomide
  • Tumorsphere

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