2. Academic Validation
  3. BCL-XL overexpression promotes tumor progression-associated properties

BCL-XL overexpression promotes tumor progression-associated properties

  • Cell Death Dis. 2017 Dec 13;8(12):3216. doi: 10.1038/s41419-017-0055-y.
Daniela Trisciuoglio 1 2,  Maria Grazia Tupone 1,  Marianna Desideri 1,  Marta Di Martile 1,  Chiara Gabellini 1 3,  Simonetta Buglioni 4,  Matteo Pallocca 5,  Gabriele Alessandrini 6,  Simona D'Aguanno 7,  Donatella Del Bufalo 8
Affiliations

Affiliations

  • 1 Preclinical Models and New Therapeutic Agents Unit, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
  • 2 Institute of Molecular Biology and Pathology, National Research Council, Via Degli Apuli 4, 00185, Rome, Italy.
  • 3 Unit of Cell and Developmental Biology, Department of Biology, University of Pisa, S.S. 12 Abetone e Brennero 4, Pisa, Italy.
  • 4 Pathology Unit, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
  • 5 SAFU Unit, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
  • 6 Thoracic Surgery Unit, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
  • 7 Preclinical Models and New Therapeutic Agents Unit, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy. [email protected].
  • 8 Preclinical Models and New Therapeutic Agents Unit, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy. [email protected].
PMID: 29238043 DOI: 10.1038/s41419-017-0055-y
Abstract

By using human melanoma and glioblastoma cell lines and their derivative BCL-XL overexpressing clones, we investigated the role of BCL-XL in aggressive features of these two tumor histotypes. We found that in both models, BCL-XL overexpression increased in vitro cell migration and invasion and facilitated tumor cells to form de novo vasculogenic structures. Furthermore, BCL-XL overexpressing cells exhibited higher tumors sphere formation capacity and expressed higher levels of some stem cell markers, supporting the concept that BCL-XL plays essential roles in the maintenance of Cancer stem cell phenotype. BCL-XL expression reduction by siRNA, the exposure to a BCL-XL-specific inhibitor and the use of a panel of human melanoma cell lines corroborated the evidence that BCL-XL regulates tumor progression-associated properties. Finally, the vascular markers and the vasculogenic mimicry were up-regulated in the BCL-XL overexpressing xenografts derived from both tumor histotypes. In conclusion, our work brings further support to the understanding of the malignant actions of BCL-XL and, in particular, to the concept that BCL-XL promotes stemness and contributes to the aggressiveness of both melanoma and glioblastoma.

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