Pleiotrophin produced by multiple myeloma induces transdifferentiation of monocytes into vascular endothelial cells: a novel mechanism of tumor-induced vasculogenesis

Chen, Haiming; Campbell, Richard A.; Chang, Yunchao; Li, Mingjie; Wang, Cathy S.; Li, Jennifer; Sanchez, Eric; Share, Michael; Steinberg, Jeffrey A.; Berenson, Ariana; Shalitin, Dror; Zeng, Zhaohui; Gui, Dorina; Pérez-Piñera, Pablo; Berenson, Ronald J.; Said, Jonathan; Bonavida, Benjamin; Deuel, Thomas F.; Berenson, James R.

doi:10.1182/blood-2008-02-133751

Cited by 86 publications

(66 citation statements)

References 62 publications

(115 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, it has been reported that the contribution of monocytes to the increased vasculature that occurs in the BM of MM patients is higher in MM patients with active disease as compared to those with MGUS or healthy subjects [33]. Recent data show that pleiothrophin production by myeloma cells induced transdifferantiation of monocytes into vascular endothelial cells in combination with macrophage colony stimulating factor (M-CSF), suggesting a critical role of this protein in vasculogenesis in MM [34].…”

Section: Vasculogenesis In MMmentioning

confidence: 99%

Angiogenesis and Multiple Myeloma

Giuliani

Storti

Bolzoni

et al. 2011

Cancer Microenvironment

View full text Add to dashboard Cite

The bone marrow microenvironment in multiple myeloma is characterized by an increased microvessel density. The production of pro-angiogenic molecules is increased and the production of angiogenic inhibitors is suppressed, leading to an "angiogenic switch". Here we present an overview of the role of angiogenesis in multiple myeloma, the pro-angiogenic factors produced by myeloma cells and the microenvironment, and the mechanisms involved in the myeloma-induced angiogenic switch. Current data suggest that the increased bone marrow angiogenesis in multiple myeloma is due to the aberrant expression of angiogenic factors by myeloma cells, the subsequent increase in pro-angiogenic activity of normal plasma cells as a result of myeloma cell angiogenic activity, and the increased number of plasma cells overall. Hypoxia also contributes to the angiogenic properties of the myeloma marrow microenvironment. The transcription factor hypoxia-inducible factor-1α is overexpressed by myeloma cells and affects their transcriptional and angiogenic profiles. In addition, potential roles of the tumor suppressor gene inhibitor of growth family member 4 and homeobox B7 have also been recently highlighted as repressors of angiogenesis and pro-angiogenic related genes, respectively. This complex pathogenetic model of myeloma-induced angiogenesis suggests that several proangiogenic molecules and related genes in myeloma cells and the microenvironment are potential therapeutic targets.

show abstract

Section: Vasculogenesis In MMmentioning

confidence: 99%

Angiogenesis and Multiple Myeloma

Giuliani

Storti

Bolzoni

et al. 2011

Cancer Microenvironment

View full text Add to dashboard Cite

show abstract

“…En outre, les polynucléaires neutrophiles et les mastocytes ont été également décrits comme des acteurs de l'angiogenèse via une action paracrine [20]. Enfin, dans le myélome multiple, les monocytes ont la capacité de se différencier en cellules endothéliales, favorisant ainsi l'angiogenèse tumorale par transdifférenciation [21].…”

Section: Les Cellules Inflammatoires Outre Les Facteurs Proangiogé-niunclassified

Vaisseaux sanguins et tumeurs ou l’art du dialogue

Azzi

Gavard

2014

Med Sci (Paris)

View full text Add to dashboard Cite

> Le réseau vasculaire joue un rôle essentiel dans le développement des cancers. Au cours de la dernière décennie, la découverte de cellules tumorales à caractère souche logées à proximité des vaisseaux sanguins a permis de mettre en lumière l'existence d'interactions fonctionnelles entre l'endothélium et les cellules tumorales. Dans cette revue, nous présentons les mécanismes d'angiogenèse, ainsi que les éléments de langage dans le dialogue établi entre la tumeur et son microenvironnement. Nous y détaillons, d'une part, les effets de la masse tumorale et son implication dans la modulation de la plasticité endothéliale et, d'autre part, la contribution de la niche vasculaire à la tumorigenèse. < précurseurs des cellules endothéliales dérivés du mésoderme et leur association en un réseau vasculaire primitif. Ce processus est principalement observé au cours des étapes précoces du dévelop-pement embryonnaire, puis lors de la vascularisation des ébauches d'organes. Par la suite, le réseau vasculaire se développe à partir de vaisseaux sanguins préexistants, principalement par prolifération et bourgeonnement des cellules endothéliales, ce qu'on appelle l'angiogenèse. Le système vasculaire forme un important réseau impliqué dans la distribution d'oxygène et de nutriments aux organes. Les cellules endothéliales qui tapissent la face interne des vaisseaux sont organisées en une fine monocouche et sont étroitement reliées entre elles par des jonctions cellulaires spécialisées. C'est cette barrière endothéliale, en interaction avec les péricytes et une matrice basale différenciée, qui définit les propriétés de la paroi vasculaire ( Figure 1A L'angiogenèse tumoraleOutre leur fonction d'échange, les vaisseaux sanguins contribuent activement aux processus de régénération et de croissance des tissus. Ces fonctions physiologiques peuvent être détournées en conditions pathologiques, notamment dans les cancers. En effet, la croissance de tumeurs solides au-delà de 1 à 2 mm 3 est dépendante du dévelop-pement d'un réseau vasculaire qui leur est consacré. L'angiogenèse

show abstract

“…In addition, carfilzomib, a proteasome inhibitor in clinical trials for the treatment of multiple myeloma, is derived from epoxomicin. 4 KMS11R did not display overt changes phenotypically as the cells maintained expression of surface CD138 as well as FGFR3 (not shown). However, the cells became resistant to epoxomicin at concentrations that are 10 times greater than the initial selecting concentration (2 nM).…”

Section: Letters To the Editormentioning

confidence: 99%

“…Furthermore, when co-injected with human MM cells into SCID (severe combined immunodeficiency) mice, human monocytes were incorporated into tumor blood vessels and expressed human vascular endothelial protein markers and genes. 4 A number of myeloma-derived chemo-attractants seem to ensure the ongoing recruitment of macrophages and monocytes that accumulate in hypoxic marrow areas, including M-CSF, VEGF and the CC-chemokines: MIP-1a, MCP-1a and others. Thus, the increased MIP-1a expression by PCs observed in our study may contribute to increased angiogenesis through the chemoattraction of such monocytes.…”

Section: Letters To the Editormentioning

confidence: 99%

“…2,3 MIP-1a is a chemoattractant for monocytes and recently it was shown that monocytes may give rise to vascular endothelium. 4 Thus, our hypothesis was that myeloma cells express MIP-1a and other chemoattractants for monocytes and macrophages, and this expression correlated with both increased bone resorption (as osteoclasts are originated from a macrophage lineage precursor cell) and increased angiogenesis. The aim of our study was to evaluate the role of MIP-1a immunoexpression on trephine biopsies in the development of myeloma bone disease and examine possible correlations between MIP-1a expression and clinical data, including prognostic factors of MM and angiogenesis.…”

mentioning

confidence: 99%

See 1 more Smart Citation