HIF1-positive and HIF1-negative glioblastoma cells compete in vitro but cooperate in tumor growth in vivo

Paolo Fiorenzo, Maria Patrizia Mongiardi, Diletta Dimitri, Mauro Cozzolino, Alberto Ferri, Nicola Montano, Gianluca Trevisi, Giulio Maira, Luca Battistini, Maria Laura Falchetti, Andrea Levi, Roberto Pallini

Research output: Contribution to journalArticle

Abstract

Glioblastoma multiforme (GBM) is characterized by extensive angiogenesis that is mostly orchestrated by the hypoxia inducible factor HIF-1. Deregulation of HIF-1 is believed to contribute to cancer initiation and progression. However, instances have been described in which loss of HIF-1 leads to more aggressive tumors. Here we investigated the consequences of downregulating HIF-1 function in the human GBM cell line TB10, both on cell proliferation in vitro and on tumor growth in vivo. RNA interference targeting the O 2-regulated HIF-1α subunit efficiently reduced HIF-1α expression and transcriptional induction of HIF-1-responsive genes without affecting cell growth. Thus, singularly grown wild-type and HIF-1α- inhibited GBM cell populations did not significantly differ in proliferation rate. However, when the two populations were co-cultured, wild-type cells overgrew the HIF-1α-inhibited cells. Subcutaneous grafting in nude mice of wild-type and HIF-1α-inhibited GBM cells lead to comparable tumor formation and growth. Interestingly, cografting of wt and HIF-1α- inhibited GBM cells in nude mice resulted in more aggressive tumors, both in terms of tumor appearance and tumor growth. This suggests that cellular populations that differ in their ability to mount a response to hypoxia may compete in vitro but cooperate in vivo resulting in increased tumor aggressiveness.

Original languageEnglish
Pages (from-to)785-791
Number of pages7
JournalInternational Journal of Oncology
Volume36
Issue number4
DOIs
Publication statusPublished - Apr 2010

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Keywords

  • Cooperation
  • Glioblastoma multiforme
  • HIF1
  • Tumor xenograft

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fiorenzo, P., Mongiardi, M. P., Dimitri, D., Cozzolino, M., Ferri, A., Montano, N., Trevisi, G., Maira, G., Battistini, L., Falchetti, M. L., Levi, A., & Pallini, R. (2010). HIF1-positive and HIF1-negative glioblastoma cells compete in vitro but cooperate in tumor growth in vivo. International Journal of Oncology, 36(4), 785-791. https://doi.org/10.3892/ijo-00000554