Open AccessJournal Article
Stromal Cell-derived Factor 1α Stimulates Human Glioblastoma Cell Growth through the Activation of Both Extracellular Signal-regulated Kinases 1/2 and Akt
Simone Barbero,Rudy Bonavia,Adriana Bajetto,Carola Porcile,Paolo Pirani,Jean Louis Ravetti,Gian Luigi Zona,Renato Spaziante,Tullio Florio,Gennaro Schettini +9 more
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TLDR
Data support a role for SDF-1alpha in the regulation of glioblastoma growth in vitro, likely through an autocrine/paracrine mechanism.Abstract:
In this paper, we describe the role of chemokine receptor CXCR4 activation by its natural ligand, the chemokine stromal cell-derived factor (SDF-1) (CXCL12), in glioblastoma cell growth in vitro. We show that both CXC chemokine receptor 4 (CXCR4) and SDF-1 mRNA are expressed in several human glioblastoma multiforme tumor tissues and in two human glioblastoma cell lines, U87-MG and DBTRG-05MG. These cells are able to secrete SDF-1 under basal conditions, and the rate of secretion is highly increased after lipopolysaccharide or 1% fetal bovine serum treatment. Exogenous SDF-1alpha induces proliferation in a dose-dependent manner in both cell lines. Moreover, we observed that SDF-1alpha-dependent proliferation is correlated with phosphorylation and activation of both extracellular signal-regulated kinases 1/2 and Akt and that these kinases are independently involved in glioblastoma cell proliferation. The role of CXCR4 stimulation in glioblastoma cell growth is further demonstrated by the ability of human monoclonal CXCR4 antibody (clone 12G5) to inhibit the SDF-1alpha-induced proliferation as well as the proliferation induced by SDF-1-releasing treatments (lipopolysaccharide and 1% fetal bovine serum). These data support a role for SDF-1alpha in the regulation of glioblastoma growth in vitro, likely through an autocrine/paracrine mechanism.read more
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Stromal fibroblasts in cancer initiation and progression
TL;DR: It is revealed that fibroblasts have a more profound influence on the development and progression of carcinomas than was previously appreciated and this has important therapeutic implications.
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Cancer and the chemokine network
TL;DR: Insight is provided into host–tumour interactions, such as the role of the leukocyte infiltrate, and into the mechanisms that determine the metastatic potential and site-specific spread of cancer cells.
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CXCL12 (SDF-1)/CXCR4 Pathway in Cancer
TL;DR: This work has shown that the CXCL12/CXCR4 axis is involved in tumor progression, angiogenesis, metastasis, and survival, and this pathway is a target for therapeutics that can block the CZC receptor 4 interaction or inhibit downstream intracellular signaling.
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Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells Involve Similar Mechanisms: Pivotal Role of the SDF-1–CXCR4 Axis
Magda Kucia,Ryan Reca,Katarzyna Miekus,Jens Wanzeck,Wojtek Wojakowski,Anna Janowska-Wieczorek,Janina Ratajczak,Mariusz Z. Ratajczak +7 more
TL;DR: It is suggested that strategies aimed at modulating the SDF‐1–CXCR4 axis could have important clinical applications both in regenerative medicine to deliver normal stem cells to the tissues/organs and in clinical hematology/oncology to inhibit metastasis of cancer stem cells.
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The significance of cancer cell expression of the chemokine receptor CXCR4
TL;DR: Preliminary data from animal models suggest that CXCR4 may be an important therapeutic target in a range of cancers, however CxCR4 plays major roles in embryogenesis, homeostasis and inflammation, which raises questions concerning the specificity of CX CR4 antagonists in the treatment of cancer.
References
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Journal ArticleDOI
Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development
TL;DR: This is the first demonstration of the involvement of a G-protein-coupled chemokine receptor in neuronal cell migration and patterning in the central nervous system and may be important for designing strategies to block HIV entry into cells and for understanding mechanisms of pathogenesis in AIDS dementia.
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The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract.
Kazunobu Tachibana,Seiichi Hirota,Hisashi Iizasa,Hisahiro Yoshida,Kenji Kawabata,Yuki Kataoka,Yukihiko Kitamura,Kouji Matsushima,Nobuaki Yoshida,Shin-Ichi Nishikawa,Tadamitsu Kishimoto,Takashi Nagasawa +11 more
TL;DR: PBSF/SDF-1 and CXCR4 define a new signalling system for organ vascularization, and it is reported that CX CR4 is expressed in developing vascular endothelial cells, and that mice lacking CxCR4 or PBSF/ sdf-1 have defective formation of the large vessels supplying the gastrointestinal tract.
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Malignant glioma: Genetics and biology of a grave matter
Elizabeth A. Maher,Frank B. Furnari,Robert M. Bachoo,David H. Rowitch,David N. Louis,Webster K. Cavenee,Ronald A. DePinho +6 more
TL;DR: Although a comprehensive view of the genetic lesions encountered in malignant gliomas has been compiled, substantive conceptual and practical barriers remain in assigning functional significance to these genetic changes and in harnessing this basic information into the development of drugs that make a difference in patient care.
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Molecular cloning and structure of a pre-B-cell growth-stimulating factor
TL;DR: A stromal cell line, PA6, was found to produce a soluble mediator, which was distinct from interleukin 7 (IL-7) and stem cell factor and supported the proliferation of a stromAL cell-dependent pre-B-cell clone, DW34.
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Interleukin-8 and human cancer biology.
TL;DR: The role and regulation of IL-8 expression in the growth and metastasis of human cancer with a focus on human pancreatic adenocarcinoma will be discussed.