NDLI: Angiopoietins Modulate Survival, Migration, and the Components of the Ang-Tie2 Pathway of Chronic Lymphocytic Leukaemia (CLL) Cells In Vitro

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Erratum to: Separation and Characterization of Epithelial and Mesenchymal-like Murine Mammary Tumor Cells Reveals Epithelial Cell Differentiation Plasticity and Enhanced Tumorigenicity of Epithelial-enriched Tumor Cells

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Angiopoietins Modulate Survival, Migration, and the Components of the Ang-Tie2 Pathway of Chronic Lymphocytic Leukaemia (CLL) Cells In Vitro

Content Provider	Springer Nature Link
Author	Aguirre Palma, Luis Mario Flamme, Hanna Gerke, Iris Kreuzer, Karl Anton
Copyright Year	2016
Abstract	In actuality, chronic lymphocytic leukaemia (CLL) remains an incurable haematopoietic malignancy of high prevalence amongst elderly populations in the West. Malignant CLL cells characteristically accumulate in the peripheral blood, bone marrow, lymph nodes, and spleen of CLL patients. There is evidence that CLL cells express Ang2 and Tie1, two central components of the Ang-Tie2 pro-angiogenic pathway. Central to blood vessel development and maintenance, at present it remains unclear how the Ang-Tie2 pathway modulates CLL pathophysiology. Here we evaluate the status of the Ang-Tie2 pathway in CLL cells and assess Ang1 levels in plasma/cell medium from CLL samples. To understand how angiopoietins in the microenvironment regulate the components of Ang-Tie2 pathway, survival, migration, and metabolic fitness of CLL cells, we exposed CLL cells to recombinant angiopoietins. CLL plasma and CLL cells in culture present significant lower levels of Ang1. CLL cells simultaneously express Ang1, Ang2, and Tie1 mRNA, but lack that of Tie2 and its regulator, VE-PTP. Exposure to Ang1 confers survival advantage in the long-term, whereas Ang2 and trebananib, an angiopoietin blocker, proved detrimental. Angiopoietins differentially modulate expression of Ang1, Ang2, and Tie1 transcripts. Ang2, but not Ang1, induces the concomitant and transient expression of Tie2 and VE-PTP mRNA. Both angiopoietins, particularly Ang2, increase CLL-Tie1 expression and Ang1 clearly induces chemotaxis and transendothelial-like migration of CLL cells. Besides, changes in caspase and ATP content corroborate the sensitivity of CLL cells to angiopoietin exposure. Altogether, this work shows that angiopoietins regulate the fate of CLL cells in a Tie2-independent manner and highlights the potential of the Ang-Tie2 pathway as a therapeutic target in CLL research.
Starting Page	13
Ending Page	26
Page Count	14
File Format	PDF
ISSN	18752292
Journal	Cancer Microenvironment
Volume Number	9
Issue Number	1
e-ISSN	18752284
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-02-05
Publisher Institution	International Cancer Microenvironment Society
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Angiogenesis CLL Angiopoietin-1 Angiopoietin-2 VE-PTP Angiogenesis-mediated migration Microenvironment Cancer Research Oncology Immunology Cell Biology Biochemistry Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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