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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Brain Neoplasms / genetics*
-
Brain Neoplasms / metabolism
-
Brain Neoplasms / pathology
-
Cell Line, Tumor
-
Cell Movement
-
Cell Proliferation
-
Disease Progression
-
Female
-
Gene Expression Regulation, Neoplastic*
-
Glioblastoma / genetics*
-
Glioblastoma / metabolism
-
Glioblastoma / pathology
-
Humans
-
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
-
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
-
Melanoma / genetics*
-
Melanoma / metabolism
-
Melanoma / pathology
-
Mice
-
Mice, Nude
-
Nanog Homeobox Protein / genetics
-
Nanog Homeobox Protein / metabolism
-
Neoplastic Stem Cells / metabolism
-
Neoplastic Stem Cells / pathology
-
Neovascularization, Pathologic / genetics*
-
Neovascularization, Pathologic / metabolism
-
Neovascularization, Pathologic / pathology
-
Octamer Transcription Factor-3 / genetics
-
Octamer Transcription Factor-3 / metabolism
-
RNA, Small Interfering / genetics
-
RNA, Small Interfering / metabolism
-
SOXB1 Transcription Factors / genetics
-
SOXB1 Transcription Factors / metabolism
-
Signal Transduction
-
Skin Neoplasms / genetics*
-
Skin Neoplasms / metabolism
-
Skin Neoplasms / pathology
-
Thiazolidines / pharmacology
-
Xenograft Model Antitumor Assays
-
bcl-X Protein / antagonists & inhibitors
-
bcl-X Protein / genetics*
-
bcl-X Protein / metabolism
Substances
-
BCL2L1 protein, human
-
HIF1A protein, human
-
Hypoxia-Inducible Factor 1, alpha Subunit
-
NANOG protein, human
-
Nanog Homeobox Protein
-
Octamer Transcription Factor-3
-
POU5F1 protein, human
-
RNA, Small Interfering
-
SOX2 protein, human
-
SOXB1 Transcription Factors
-
Thiazolidines
-
bcl-X Protein