Retrovirus-transformed erythroleukemia cells induce central nervous system failure in a new syngeneic mouse model of meningeal leukemia

MacPherson, Gordon; Hanson, Charlotte; Thompson, Delores; Perella, Christine M.; Cmarik, Joan L.; Ruscetti, Sandra K.

doi:10.1016/j.leukres.2011.08.019

Cited by 2 publications

(1 citation statement)

References 39 publications

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“…High VEGF-A levels in the cerebrospinal fluid of leukemia patients have been implicated in CNS metastasis [271]. In ALL xenograft and syngeneic mouse leukemia in vivo models, VEGF-A produced by leukemia cells was required for their trans-endothelial migration and penetration into the CNS [272,273].…”

Section: Tumor Type Metastatic Sites Vegfr-1 Ligands Vegfr-1mentioning

confidence: 99%

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Ceci

Atzori

Lacal

et al. 2020

IJMS

175

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The vascular endothelial growth factor (VEGF) family members, VEGF-A, placenta growth factor (PlGF), and to a lesser extent VEGF-B, play an essential role in tumor-associated angiogenesis, tissue infiltration, and metastasis formation. Although VEGF-A can activate both VEGFR-1 and VEGFR-2 membrane receptors, PlGF and VEGF-B exclusively interact with VEGFR-1. Differently from VEGFR-2, which is involved both in physiological and pathological angiogenesis, in the adult VEGFR-1 is required only for pathological angiogenesis. Besides this role in tumor endothelium, ligand-mediated stimulation of VEGFR-1 expressed in tumor cells may directly induce cell chemotaxis and extracellular matrix invasion. Furthermore, VEGFR-1 activation in myeloid progenitors and tumor-associated macrophages favors cancer immune escape through the release of immunosuppressive cytokines. These properties have prompted a number of preclinical and clinical studies to analyze VEGFR-1 involvement in the metastatic process. The aim of the present review is to highlight the contribution of VEGFs/VEGFR-1 signaling in the progression of different tumor types and to provide an overview of the therapeutic approaches targeting VEGFR-1 currently under investigation.

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Section: Tumor Type Metastatic Sites Vegfr-1 Ligands Vegfr-1mentioning

confidence: 99%

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Ceci

Atzori

Lacal

et al. 2020

IJMS

175

View full text Add to dashboard Cite

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Central nervous system involvement in acute lymphoblastic leukemia is mediated by vascular endothelial growth factor

Münch

Trentin²,

Herzig³

et al. 2017

Blood

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In acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is a major clinical concern. Despite nondetectable CNS leukemia in many cases, prophylactic CNS-directed conventional intrathecal chemotherapy is required for relapse-free survival, indicating subclinical CNS manifestation in most patients. However, CNS-directed therapy is associated with long-term sequelae, including neurocognitive deficits and secondary neoplasms. Therefore, molecular mechanisms and pathways mediating leukemia-cell entry into the CNS need to be understood to identify targets for prophylactic and therapeutic interventions and develop alternative CNS-directed treatment strategies. In this study, we analyzed leukemia-cell entry into the CNS using a primograft ALL mouse model. We found that primary ALL cells transplanted onto nonobese diabetic/severe combined immunodeficiency mice faithfully recapitulated clinical and pathological features of meningeal infiltration seen in patients with ALL. ALL cells that had entered the CNS and were infiltrating the meninges were characterized by high expression of vascular endothelial growth factor A (). Although cellular viability, growth, proliferation, and survival of ALL cells were found to be independent of VEGF, transendothelial migration through CNS microvascular endothelial cells was regulated by VEGF. The importance of VEGF produced by ALL cells in mediating leukemia-cell entry into the CNS and leptomeningeal infiltration was further demonstrated by specific reduction of CNS leukemia on in vivo VEGF capture by the anti-VEGF antibody bevacizumab. Thus, we identified a mechanism of ALL-cell entry into the CNS, which by targeting VEGF signaling may serve as a novel strategy to control CNS leukemia in patients, replacing conventional CNS-toxic treatment.

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Retrovirus-transformed erythroleukemia cells induce central nervous system failure in a new syngeneic mouse model of meningeal leukemia

Cited by 2 publications

References 39 publications

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Central nervous system involvement in acute lymphoblastic leukemia is mediated by vascular endothelial growth factor

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