Vascular endothelial growth factor A (<scp>VEGFA</scp>) expression in mycosis fungoides

Pileri, Alessandro; Agostinelli, Claudio; Righi, Simona; Fuligni, Fabio; Bacci, Francesco; Sabattini, Elena; Patrizi, Annalisa; Pileri, Stefano; Piccaluga, Pier Paolo

doi:10.1111/his.12445

Cited by 19 publications

(26 citation statements)

References 50 publications

(99 reference statements)

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“…The malignant T cells also display aberrant release of cytokines and other factors, such as vascular endothelial growth factor (VEGF), prostaglandins, and lymphotoxins, which promote activation of endothelial cells and fibroblasts, thereby stimulating angiogenesis via both direct and indirect mechanisms [62, 70, 71, 81, 119, 133, 134]. For example, the malignant T cells can trough release of VEGF-A and lymphotoxin α induce enhanced endothelial sprouting in vitro and further trigger fibroblast expression of VEGF-C and angiogenesis in vivo , supporting the concept that the malignant T cells orchestrate profound changes in the tumor microenvironment [133, 135].…”

Section: The Malignant T Cells Foster Pro-tumorigenic Inflammation Thmentioning

confidence: 99%

Malignant inflammation in cutaneous T‐cell lymphoma—a hostile takeover

et al. 2016

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Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term “malignant inflammation” as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL.

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Section: The Malignant T Cells Foster Pro-tumorigenic Inflammation Thmentioning

confidence: 99%

Malignant inflammation in cutaneous T‐cell lymphoma—a hostile takeover

et al. 2016

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“…In this respect, several studies have demonstrated increased angiogenesis in MF and SS . Angiogenesis is accompanied by enhanced expression of angiogenic molecules in both entities . These angiogenic molecules include VEGF‐A, VEGF‐C, and angiopoietin‐2, all pivotal molecules during tumor angiogenesis that may considerably alter the metastatic niche for SC in the skin.…”

Section: The Enigma Of Skin Homing: a Novel Therapeutic Avenue?mentioning

confidence: 99%

Sézary syndrome: old enigmas, new targets

Nicolay

Felcht

Schledzewski

et al. 2016

J Deutsche Derma Gesell

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Summary Sézary syndrome, the leukemic variant of cutaneous T‐cell lymphoma, is still an enigmatic disease with a fatal prognosis. Recent research, however, has identified a multitude of dysregulated molecular pathways that contribute to malignant transformation and therapy resistance of Sézary cells (SC). With respect to T‐cell development, SC either represent naive T cells, T effector memory or T central memory cells. Functionally, SC may differentiate into Th2, Treg, or even Th17 cells. Despite their plasticity, SC express characteristic diagnostic marker proteins including CD158k, CD164, FcRL3, and PD‐1 as well as skin‐homing receptors such as CLA and CCR4. Already tested in (pre)clinical trials, CD158k, PD‐1, CTLA‐4, and CCR4 also represent promising therapeutic targets. Molecular alterations in SC include transcription factors such as STAT3, 4, and 5, as well as TWIST1 and TOX. TWIST1 induces expression of DNM3os containing the miR‐199a2/214 cluster, a key hub controlling multiple cancer networks. In addition, activation of NFκB and the MAPK pathway as well as altered TCR signaling cause apoptosis resistance. Recently, whole genome and exome sequencing has revealed somatic copy number variations as predominant mutations in SC, primarily affecting apoptosis, NFκB signaling, DNA integrity, and T‐cell activation. In order to facilitate development of novel therapies, improved in vivo models, which better reflect the pathogenesis and clinical course of Sézary syndrome, are currently being generated.

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“…In diesem Zusammenhang wurde bei einigen Untersuchungen verstärkte Angiogenese bei MF und SS beobachtet . Die Angiogenese ist bei beiden Entitäten von der erhöhten Expression angiogenetischer Moleküle begleitet . Hierzu gehören VEGF‐A, VEGF‐C und Angiopoietin‐2, die alle bei der Tumorangiogenese eine entscheidende Rolle spielen und die Metastasierungsnische für SC in der Haut deutlich verändern können.…”

Section: Das Rätsel Des Homing In Die Haut: Eine Neue Therapeutische unclassified

Sézary‐Syndrom: von ungelösten Fragen zu neuen Therapieansätzen

Nicolay

Felcht

Schledzewski

et al. 2016

J Deutsche Derma Gesell

View full text Add to dashboard Cite

Sézary syndrome, the leukemic variant of cutaneous T-cell lymphoma, is still an enigmatic disease with a fatal prognosis. Recent research, however, has identified a multitude of dysregulated molecular pathways that contribute to malignant transformation and therapy resistance of Sézary cells (SC). With respect to T-cell development, SC either represent naive T cells, T effector memory or T central memory cells. Functionally, SC may differentiate into Th2, Treg, or even Th17 cells. Despite their plasticity, SC express characteristic diagnostic marker proteins including CD158k, CD164, FcRL3, and PD-1 as well as skin-homing receptors such as CLA and CCR4. Already tested in (pre)clinical trials, CD158k, PD-1, CTLA-4, and CCR4 also represent promising therapeutic targets. Molecular alterations in SC include transcription factors such as STAT3, 4, and 5, as well as TWIST1 and TOX. TWIST1 induces expression of DNM3os containing the miR-199a2/214 cluster, a key hub controlling multiple cancer networks. In addition, activation of NFκB and the MAPK pathway as well as altered TCR signaling cause apoptosis resistance. Recently, whole genome and exome sequencing has revealed somatic copy number variations as predominant mutations in SC, primarily affecting apoptosis, NFκB signaling, DNA integrity, and T-cell activation. In order to facilitate development of novel therapies, improved in vivo models, which better reflect the pathogenesis and clinical course of Sézary syndrome, are currently being generated.

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Vascular endothelial growth factor A (VEGFA) expression in mycosis fungoides

Abstract: For the first time, we demonstrate VEGFA expression in MF cells, suggesting that the VEGF pathway may be implicated in MF pathogenesis and can represent a novel therapeutic target.

Cited by 19 publications

References 50 publications

Malignant inflammation in cutaneous T‐cell lymphoma—a hostile takeover

Malignant inflammation in cutaneous T‐cell lymphoma—a hostile takeover

Sézary syndrome: old enigmas, new targets

Sézary‐Syndrom: von ungelösten Fragen zu neuen Therapieansätzen

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