Increased expression of vascular endothelial growth factor receptor 1 correlates with VEGF and microvessel density in Philadelphia chromosome-negative myeloproliferative neoplasms

AimsThe authors investigated vascular endothelial growth factor receptor 1 (VEGFR-1) protein expression in a series of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPNs) and its correlations with microvessel density (MVD) and vascular endothelial growth factor (VEGF).Methods83 bone marrow biopsies of Ph- MPNs patients, including 27 essential thrombocythaemia (ET), 21 polycythaemia vera (PV) and 35 primary myelofibrosis (PMF), and 10 normal controls (NCs) were investigated by immunohistochemistry.ResultsPatients with PV and PMF showed an increased MVD (PV: 20.1±10.6; PMF: 25.8±6.5) compared with those with ET or NCs (ET: 10.4±4.6; NCs: 7±3.4). VEGFR-1 expression was increased in Ph- MPNs, particularly in PV and PMF (NCs: 0.07±0.03; ET: 0.15±0.09; PV: 0.31±0.2; PMF: 0.31±0.04). VEGF expression parallelled VEGFR-1 and resulted increased in Ph- MPNs (NCs: 0.08±0.04; ET: 0.13±0.06; PV: 0.29±0.2; PMF: 0.31±0.15) and higher in post-polycythaemic myelofibrosis and in the fibrotic stage of PMF than in the non-fibrotic phases of both diseases. VEGFR-1 protein expression correlated with MVD and VEGF expression in Ph- MPNs. VEGFR-1 and VEGF were expressed by the same bone marrow populations: megakaryocytes, macrophages and immature myeloid precursors showed a moderate to strong immunostaining intensity in both Ph- MPNs and NCs. The erythroid precursors were not immunoreactive.ConclusionsVEGFR-1 and VEGF were increased and co-localised in megakaryocytes, macrophages and myeloid precursors of Ph- MPNs. This finding supports the hypothesis of a VEGF/VEGFR-1 autocrine loop in the neoplastic cells of Ph- MPNs.

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Vascular endothelial growth factor receptor 1 (VEGFR1) tyrosine kinase signaling facilitates granulation tissue formation with recruitment of VEGFR1+ cells from bone marrow

Anatomical Science International ◽

10.1007/s12565-017-0424-8 ◽

2017 ◽

Vol 93 (3) ◽

pp. 372-383 ◽

Cited By ~ 4

Author(s):

Keiichi Park ◽

Hideki Amano ◽

Yoshiya Ito ◽

Yoshio Mastui ◽

Mariko Kamata ◽

...

Keyword(s):

Bone Marrow ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Granulation Tissue ◽

Growth Factor Receptor ◽

Vascular Endothelial ◽

Tissue Formation ◽

Tyrosine Kinase Signaling ◽

Granulation Tissue Formation ◽

Endothelial Growth Factor

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Clinical and Histopathological Parameters Correlate with Microvessel Density but Not with Vascular Endothelial Growth Factor Expression in Ovarian Cancer

Revista de Chimie ◽

10.37358/rc.18.5.6283 ◽

2018 ◽

Vol 69 (5) ◽

pp. 1173-1178

Author(s):

Laurentiu Pirtea ◽

Dorin Grigoras ◽

Cristina Secosan ◽

Ioan Sas ◽

Razvan Ilina ◽

...

Keyword(s):

Ovarian Cancer ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Microvessel Density ◽

Clinicopathological Parameters ◽

Clinical Parameters ◽

Vascular Endothelial ◽

Vegf Expression ◽

Ovarian Carcinomas ◽

Endothelial Growth Factor

Ovarian cancer malignancies have the worst prognosis among all gynecological malignancies. As angiogenesis represents a key step for tumor progression, vascular endothelial growth factor (VEGF) is one of the most discussed pro-angiogenic factors. VEGF expression was investigated in 62 cases of ovarian carcinomas. Microvessel density (MVD) was evaluated by correlating the results with clinical and histopathological parameters. Because of the controversial results reported in other studies, VEGF was assessed together with MVD. Our results suggest a more complex angiogenic mechanism in ovarian cancer based on the discrepancies between VEGF expression, microvessel density and their correlation with clinical parameters. The conflicting data arising from this study supports the implications of different growth factors, others than VEGF in ovarian cancer. This hypothesis is sustained by the lack of correlation between VEGF and clinical parameters, and by the significant correlation between microvessel density and clinicopathological parameters. Thus, further studies are needed for a complete evaluation of angiogenesis in ovarian cancer.

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Bevacizumab Reduces VEGF Expression in Patients with Relapsed and/or Refractory Acute Myeloid Leukaemia (AML) without Clinical Antileukemic Activity.

Blood ◽

10.1182/blood.v108.11.4543.4543 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4543-4543

Author(s):

Lejla Zahiragic ◽

Christoph Schliemann ◽

Ralf Bieker ◽

Wolfgang E. Berdel ◽

Rolf M. Mesters

Keyword(s):

Bone Marrow ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Wilcoxon Test ◽

Vascular Endothelial ◽

Antileukemic Activity ◽

Vegf Expression ◽

Wide Range ◽

Endothelial Growth Factor ◽

Refractory Aml

Abstract Angiogenesis is required for tumor growth and metastasis and is an attractive target for cancer therapy. Because of its pivotal role in tumorassociated angiogenesis across a wide range of malignancies, vascular endothelial growth factor-A (VEGF-A) has emerged as a central therapeutic target in cancer. Neoangiogenesis has been shown to play an important role in the pathogenesis of AML (Padro et al., Blood 2000) and antiangiogenic therapy could constitute a novel strategy for its treatment (Mesters et al., Blood 2001). Autocrine and paracrine secretion of vascular endothelial growth factor (VEGF) in the bone marrow may promote proliferation and survival of leukemic blasts (Fiedler et al., Blood 1997). This concept represented the rationale for the therapeutic application of bevacizumab (BV), a recombinant humanised monoclonal antibody against VEGF, in patients with advanced AML after failure of standard treatment. Nine patients (median age 63 years; range 46–81 years) with relapsed and/or refractory AML not judged medically fit for further intensive chemotherapy were enrolled in this study. All patients received at least one cycle of BV (10 mg/kg body weight), 5 patients received 2 cycles (days 1 and 14) and 2 patients a 3rd cycle (day 35). Treatment was well tolerated, without treatment-related side effects. Two patients had to be withdrawn from drug administration after cycle one due to progressive disease. After treatment with BV none of the patients fulfilled the criteria of a partial response, defined as the clearance of at least 50 % marrow blasts accompanied by increases in platelet counts and haemoglobin values. The level of VEGF expression in the bone marrow determined by immunohistochemistry significantly decreased during treatment with BV (before BV treatment: median of 3.78 arbitrary units (AU) [range 1.5–5.8 AU]; after BV treatment: median of 2.57 AU [range 1.3–5.0 AU]; Wilcoxon test, P<0.05). In contrast, VEGFR-2 expression by leukemic blasts and bone marrow microvessel density did not change significantly. In conclusion, single agent BV has no significant antileukemic activity in relapsed and/or refractory AML.

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