Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma

Scavelli, Claudio; Nico, Beatrice; Cirulli, Teresa; Ria, Roberto; Pietro, Giulia Di; Mangieri, Domenica; Bacigalupo, Andrea; Mangialardi, Giuseppe; Coluccia, Addolorata Maria Luce; Caravita, Tommaso; Molica, Stefano; Dammacco, Franco; Vacca, Angelo

doi:10.1038/sj.onc.1210691

Cited by 128 publications

(118 citation statements)

References 42 publications

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“…In this way high-grade tumors can mimic an endothelial-like phenotype and participate in the formation of vascular-like structures, which could contribute to tumor perfusion and eventually tumor metastasis (Maniotis et al, 1999). This form of tumor cell plasticity was termed vasculogenic mimicry and it has been described in several tumor types, such as melanoma, Ewing sarcoma, ovarian and breast cancer, and multiple myeloma (Maniotis et al, 1999;Sharma et al, 2002;Shirakawa et al, 2002;van der Schaft et al, 2005;Scavelli et al, 2008). Melanoma cells were shown to participate in neovascularization in a circulation-deficient muscle microenvironment in vivo (Hendrix et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Critical role of endoglin in tumor cell plasticity of Ewing sarcoma and melanoma

et al. 2010

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Tumor cell plasticity enables certain types of highly malignant tumor cells to dedifferentiate and engage a plastic multipotent embryonic-like phenotype, which enables them to 'adapt' during tumor progression and escape conventional therapeutic strategies. This plastic phenotype of aggressive cancer cells enables them to express endothelial cell-specific markers and form tubelike structures, a phenotype that has been linked to aggressive behavior and poor prognosis. We demonstrate here that the transforming growth factor (TGF)-b coreceptor endoglin, an endothelial cell marker, is expressed by tumor cells and its expression correlates with tumor cell plasticity in two types of human cancer, Ewing sarcoma and melanoma. Moreover, endoglin expression was significantly associated with worse survival of Ewing sarcoma patients. Endoglin knockdown in tumor cells interferes with tumor cell plasticity and reduces invasiveness and anchorage-independent growth in vitro. Ewing sarcoma and melanoma cells with reduced endoglin levels showed reduced tumor growth in vivo. Mechanistically, we provide evidence that endoglin, while interfering with TGF-b signaling, is required for efficient bone morphogenetic protein, integrin, focal adhesion kinase and phosphoinositide-3-kinase signaling in order to maintain tumor cell plasticity. The present study delineates an important role of endoglin in tumor cell plasticity and progression of aggressive tumors.

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Section: Introductionmentioning

confidence: 99%

Critical role of endoglin in tumor cell plasticity of Ewing sarcoma and melanoma

et al. 2010

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“…Thus, macrophage involvement in the vasculogenic pathway proceeds in step with MM activity, and with progression of plasma cell tumors as well. 18 Overall, these data suggest that in active MM, macrophages contribute to neovascularization through a vasculogenic pathway.…”

mentioning

confidence: 86%

“…18 By contrast, macrophages from non-active MM, monoclonal gammopathies of undetermined significance and benign anemia patients display similar, albeit weaker features. Endothelial cell-like macrophages and apparently typical macrophages contribute sizeably to the formation of the neovessel wall in patients with active MM, whereas their vascular supply is minimal in non-active MM, and absent in MGUS patients and control patients.…”

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confidence: 99%

“…Endothelial cell-like macrophages and apparently typical macrophages contribute sizeably to the formation of the neovessel wall in patients with active MM, whereas their vascular supply is minimal in non-active MM, and absent in MGUS patients and control patients. 18 In patients with active MM, fluorescence-activated cell sorting (FACS) analyses on freshly isolated bone marrow mononuclear cells showed higher percentages of CD14/CD68 double-positive cells than in those with nonactive disease and MGUS. Furthermore, in active MM patients, bone marrow biopsies displayed macrophages with both endothelial cell-like (that is, CD68/FVIII-RA double positive) and apparently typical (that is, CD68 positive/FVIII-RA negative) features located in the microvessel wall and collaborating with MM endothelial cells to line the vessel lumen.…”

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confidence: 99%

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The role of monocytes-macrophages in vasculogenesis in multiple myeloma

Ribatti

Vacca

2009

Leukemia

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“…The activated TAMs can release various niche factors, such as growth factors, chemokines, and proteolytic enzymes to promote TME formation. Bone marrow-derived monocytes and macrophages contribute to vasculogenesis in multiple myeloma, and bone marrow macrophages from multiple myeloma patients can form a capillarylike network and contribute to the malignancy of multiple myeloma [89,90]. In addition, Tie2-expressing monocytes have nonredundant function to promote tumor angiogenesis and genesis of TME in mice [88].…”

Section: Chronic Inflammation and Tumor Microenvironmentmentioning

confidence: 99%

Deciphering the Key Features of Malignant Tumor Microenvironment for Anti-cancer Therapy

Shang

Zhang

Pan

et al. 2012

Cancer Microenvironment

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Tumor microenvironment (TME) is important in tumor development and may be a target for anti-cancer therapy. The genesis of TME is a dynamic process that is regulated by intrinsic and extrinsic factors and coordinated by multiple genes, cells, and signal pathways. Cancer anaerobic metabolism and various oncogenes may stimulate the genesis of TME. Tumor cells and cancer stem cells actively participate in the genesis of the cancer stem cell niche and tumor neovascularization, important in the initiation of the TME. Various cancer-associated stromal cells, derived niche factors, and tumor-associated macrophages may function as promoters in the genesis of the TME. Dicer1 gene-deleted stromal cells can induce generation of cancer stem cells and initiate tumorigenesis, suggesting that stromal cells also may promote the genesis of the TME. Therefore, the key features of TME include niche-driving oncogenes, cancer anaerobic metabolism, niche-driving cancer stem cells, neovascularization, tumor-associated inflammatory cells, and cancer-associated stromal cells. These features are potential targets for normalization of the malignant TME and effective anti-cancer therapy.

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Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma

Cited by 128 publications

References 42 publications

Critical role of endoglin in tumor cell plasticity of Ewing sarcoma and melanoma

Critical role of endoglin in tumor cell plasticity of Ewing sarcoma and melanoma

The role of monocytes-macrophages in vasculogenesis in multiple myeloma

Deciphering the Key Features of Malignant Tumor Microenvironment for Anti-cancer Therapy

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