Expression of FLT4 and its ligand VEGF-C in acute myeloid leukemia

Fielder, W; Graeven, Ullrich; Ergün, Süleyman; Verago, Sandra; Kilic, Nerbil; Stockschläder, M; Hossfeld, Dieter K.

doi:10.1038/sj.leu.2400722

Cited by 100 publications

(82 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In agreement with our results, expression of VEGFR-3 has been reported in some hematopoietic and leukemia cells. 62,63 Furthermore, we observed increased densities of peritumoral macrophages in the skin surrounding VEGF-C-transfected melanomas. Enhanced host-tumor defense capabilities by increased recruitment of macrophages may explain the observed growth impediment of VEGF-C-overexpressing melanomas, because increased densities of peritumoral macrophages were correlated with the extent of tumor growth suppression.…”

Section: Discussionmentioning

confidence: 75%

Concurrent Induction of Lymphangiogenesis, Angiogenesis, and Macrophage Recruitment by Vascular Endothelial Growth Factor-C in Melanoma

Skobe

Hamberg

Hawighorst

et al. 2001

The American Journal of Pathology

350

322

View full text Add to dashboard Cite

Interactions of tumor cells with lymphatic vessels are of paramount importance for tumor progression, however, the underlying molecular mechanisms are poorly understood. Whereas enlarged lymphatic vessels are frequently observed at the periphery of malignant melanomas, it has remained unclear whether intratumoral lymphangiogenesis occurs within these tumors. Here, we demonstrate the presence of intratumoral lymphatics and enlargement of lymphatic vessels at the tumor periphery in vascular endothelial growth factor (VEGF)-C-overexpressing human melanomas transplanted onto nude mice. VEGF-C expression also resulted in enhanced tumor angiogenesis, indicating a coordinated regulation of lymphangiogenesis and angiogenesis in melanoma progression. The specific biological effects of VEGF-C were critically dependent on its proteolytic processing in vivo.

show abstract

Section: Discussionmentioning

confidence: 75%

Concurrent Induction of Lymphangiogenesis, Angiogenesis, and Macrophage Recruitment by Vascular Endothelial Growth Factor-C in Melanoma

Skobe

Hamberg

Hawighorst

et al. 2001

The American Journal of Pathology

350

322

View full text Add to dashboard Cite

show abstract

“…Fielder et al (1997) reported that leukaemic cells expressed VEGF-C in most of the AML patients. Dias et al (2002) found that VEGF-C that was released from the endothelium could induce leukaemic cell proliferation, promote their survival, and protect them from chemotherapy-induced apoptosis.…”

Section: Angio-indexmentioning

confidence: 99%

“…Compared to the levels in the control, increased plasma levels of VEGF-A obtained from peripheral blood (PB) were observed in AML patients (Aguayo et al, 2000(Aguayo et al, , 2002. Elevated VEGF-C expression was reported in patients with prostatic carcinoma and oesophageal squamous cell carcinoma (Tsurusaki et al, 1999;Kitadai et al, 2001) but is controversial with regard to AML patients (Fielder et al, 1997;Dias et al, 2002;Loges et al, 2005). In contrast, decreased VEGF-D expression levels were reported in patients with lung adenocarcinoma and colorectal carcinoma (Niki et al, 2000;Onogawa et al, 2004).…”

mentioning

confidence: 99%

Marrow angiogenesis-associated factors as prognostic biomarkers in patients with acute myelogenous leukaemia

Tien

et al. 2007

Br J Cancer

View full text Add to dashboard Cite

Bone marrow (BM) neoangiogenesis plays an important role in acute myelogenous leukaemia (AML), and depends on the interplay of members of the vascular endothelial growth factor (VEGF) and angiopoietin (Ang) families. We determined the marrow levels of seven molecules associated with angiogenesis in 52 AML patients before chemotherapy and 20 healthy controls: VEGF-A, VEGF/PlGF, VEGF-C, VEGF-D, Ang-1, Ang-2, and Tie-2. All the molecules were quantified using enzyme-linked immunosorbent assay (ELISA). Comparing to normal controls, the marrow levels of VEGF/PlGF, Ang-2, and Tie-2 were significantly higher, and those of VEGF-C and Ang-1 were significantly lower in the AML patients ( P <0.001). A total of 31 patients were further subjected to survival analysis. Patients with lower Tie-2 (<26 ng ml −1 ) and Ang-2 levels (<4500 pg ml −1 ) displayed a survival advantage ( P =0.037 and 0.042, respectively), same as patients with higher VEGF/PlGF (⩾1 pg ml −1 ) and VEGF-D levels (⩾350 pg ml −1 ) ( P =0.020 and 0.016, respectively). An angio-index ((Ang-2 × Tie-2)/(VEGF/PlGF × VEGF-D)) was established and multivariate Cox regression analysis revealed that patients with higher angio-index values (⩾50) displayed poor prognosis (hazard ratio 5.91, 95% confidence interval 1.99–17.56; P =0.001). The angio-index is closely associated with the clinical outcome of AML patients and may be valuable in disease prognosis.

show abstract

“…VEGF type C, another member of the vascular endothelial growth factor family, is expressed by leukemic blasts in a significant proportion of patients with AML. 33 VEGFR-2 was thought to be exclusively expressed by adult endothelial cells. However, it has recently been shown that VEGFR-2 is present on a subset of primitive hematopoietic stem cells 34 as well as on some leukemic cell lines and isolated blasts from AML patients.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of vascular endothelial growth factor (VEGF) and its cellular receptor KDR (VEGFR-2) in the bone marrow of patients with acute myeloid leukemia

et al. 2002

View full text Add to dashboard Cite

Vascular endothelial growth factor (VEGF) and its cellular receptor VEGFR-2 have been implicated as the main endothelial pathway required for tumor neovascularization. However, the importance of the VEGF/VEGFR-2 system for angiogenesis in hematologic malignancies such as AML remains to be elucidated. In 32 patients with newly diagnosed untreated AML, we observed by immunohistochemical analysis of bone marrow biopsies significantly higher levels of VEGF and VEGFR-2 expression than in 10 control patients (P Ͻ0.001). In contrast, VEGFR-1 staining levels in AML patients were in the same range as in the controls. Expression of VEGF and VEGFR-2 was significantly higher in patients with a high degree of microvessel density compared to those with a low degree (VEGF: P ‫;420.0؍‬ VEGFR-2: P ‫)040.0؍‬ and correlated well with bone marrow microvessel density (r s ‫665.0؍‬ and 0.609, respectively; P Ͻ0.001). Furthermore, in patients who achieved a complete remission following induction chemotherapy VEGFR-2 staining levels decreased into the normal range. In conclusion, our results provide evidence for increased expression of VEGF/VEGFR-2 of leukemic blasts and correlation with angiogenesis in the bone marrow of AML patients. Thus, VEGF/VEGFR-2 might constitute promising targets for antiangiogenic and antileukemic treatment strategies in AML.

show abstract

Expression of FLT4 and its ligand VEGF-C in acute myeloid leukemia

Abstract: mononuclear cells

Cited by 100 publications

References 2 publications

Concurrent Induction of Lymphangiogenesis, Angiogenesis, and Macrophage Recruitment by Vascular Endothelial Growth Factor-C in Melanoma

Concurrent Induction of Lymphangiogenesis, Angiogenesis, and Macrophage Recruitment by Vascular Endothelial Growth Factor-C in Melanoma

Marrow angiogenesis-associated factors as prognostic biomarkers in patients with acute myelogenous leukaemia

Overexpression of vascular endothelial growth factor (VEGF) and its cellular receptor KDR (VEGFR-2) in the bone marrow of patients with acute myeloid leukemia

Contact Info

Product

Resources

About