Vascular endothelial growth factor and its receptors in multiple myeloma

Ria, Roberto; Roccaro, Aldo M.; Merchionne, Francesca; Vacca, Angelo; Dammacco, Franco; Ribatti, Doménico

doi:10.1038/sj.leu.2403076

Cited by 63 publications

(43 citation statements)

References 76 publications

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“…The key mechanism involved in such effect was the inhibition of angiogenesis, which caused ischemic necrosis in the tumors. IL-27 induced the downregulation of different proangiogenic molecules, including some MM growth factors, such as IL-6, VEGF-D, and CCL2 (40,41). Although VEGF-D and CCL2 were downregulated in tumors formed in IL-27-treated mice and in IL-27 in vitro treated primary MM cells, IL-6 was not detected in primary MM cells.…”

Section: Discussionmentioning

confidence: 90%

“…Here, we showed that human primary MM cells expressed functional IL-27R, and IL-27 triggering affected their angiogenic activity, whereas it did not attract tumor cells in chemotaxis assays nor affected their apoptosis, proliferation, or cytokine release. IL-27 influenced the expression of a wide panel of angiogenesisrelated genes and inhibited different proangiogenic factors such as VEGF-D and CCL2, two of the major MM growth factors (40,41).…”

Section: Discussionmentioning

confidence: 99%

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Interleukin-27 Acts as Multifunctional Antitumor Agent in Multiple Myeloma

Cocco

Giuliani

Carlo

et al. 2010

Clinical Cancer Research

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Purpose: Multiple myeloma (MM) derives from plasmablast/plasma cells that accumulate in the bone marrow. Different microenvironmental factors may promote metastatic dissemination especially to the skeleton, causing bone destruction. The balance between osteoclast and osteoblast activity represents a critical issue in bone remodeling. Thus, we investigated whether interluekin-27 (IL-27) may function as an antitumor agent by acting directly on MM cells and/or on osteoclasts/osteoblasts.Experimental Design: The IL-27 direct antitumor activity on MM cells was investigated in terms of angiogenesis, proliferation, apoptosis, and chemotaxis. The IL-27 activity on osteoclast/osteoblast differentiation and function was also tested. In vivo studies were done using severe combined immunodeficient/nonobese diabetic mice injected with MM cell lines. Tumors from IL-27-and PBS-treated mice were analyzed by immunohistochemistry and PCR array.Results: We showed that IL-27 (a) strongly inhibited tumor growth of primary MM cells and MM cell lines through inhibition of angiogenesis, (b) inhibited osteoclast differentiation and activity and induced osteoblast proliferation, and (c) damped in vivo tumorigenicity of human MM cell lines through inhibition of angiogenesis.Conclusions: These findings show that IL-27 may represent a novel therapeutic agent capable of inhibiting directly MM cell growth as well as osteoclast differentiation and activity. Clin Cancer Res; 16(16); 4188-97. ©2010 AACR.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Interleukin-27 Acts as Multifunctional Antitumor Agent in Multiple Myeloma

Cocco

Giuliani

Carlo

et al. 2010

Clinical Cancer Research

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“…It has been demonstrated that myeloma cells directly produce VEGF [37][38][39]. Moreover, VEGF produced by myeloma cells stimulates interleukin-6 (IL-6) and VEGF secretion by BM stromal cells that in turn induce VEGF production by myeloma cells in a paracrine fashion [40,41].…”

Section: Vascular Endothelial Growth Factor (Vegf)mentioning

confidence: 99%

Angiogenesis and Multiple Myeloma

Giuliani

Storti

Bolzoni

et al. 2011

Cancer Microenvironment

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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.

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“…Several studies show overexpression and secretion of vascular endothelial growth factor (VEGF) by the clonal plasma cells (Ria et al, 2003). Vascular endothelial growth factor stimulates proliferation and chemotaxis in both endothelial cells (EC) via VEGF receptor-2 (VEGFR-2) and stromal cells via VEGFR-1.…”

Section: Angiogenesis In Multiple Myelomamentioning

confidence: 99%

Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma

2006

Self Cite

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Tumor microenvironment is essential for tumor cell proliferation, angiogenesis, invasion and metastasis through its provision of survival signals, secretion of growth and pro-angiogenic factors, and direct adhesion molecule interactions. This review examines its importance in the induction of an angiogenic response in multiple myeloma (MM). The encouraging results of preclinical and clinical trials in which MM has been treated by targeting the tumor microenvironment are also discussed.

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Vascular endothelial growth factor and its receptors in multiple myeloma

Cited by 63 publications

References 76 publications

Interleukin-27 Acts as Multifunctional Antitumor Agent in Multiple Myeloma

Interleukin-27 Acts as Multifunctional Antitumor Agent in Multiple Myeloma

Angiogenesis and Multiple Myeloma

Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma

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