Mechanisms of vascularization in murine models of primary and metastatic tumor growth

Bugyik, Edina; Rényi-Vámos, F; Szabó, V.; Dezső, Katalin; Ecker, Nora; Rókusz, András; Nagy, Péter; Döme, Balázs; Paku, Sándor

doi:10.1186/s40880-016-0083-5

Cited by 36 publications

(16 citation statements)

References 22 publications

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“…Previous studies of MVD as a potential predictive marker have given conflicting results [17,18,48]. A recent review on anti-angiogenic therapies by Bugyik et al proposes that the focus should be on patients where primary tumours have endothelial proliferation [49]. We found that proliferating vessels, expressed as VPI, have a stronger impact on prognosis than vessel density itself, and we propose that further studies on the predictive impact of VPI are needed.…”

Section: Discussionmentioning

confidence: 68%

Microvascular proliferation is associated with aggressive tumour features and reduced survival in lung adenocarcinoma

Ramnefjell

Aamelfot

Aziz

et al. 2017

The Journal of Pathology CR

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Despite new treatment options in lung cancer, there is still a need for better biomarkers to assist in therapy decisions. Angiogenesis has been associated with tumour growth and dissemination, and the vascular proliferation index (VPI) is a valuable prognostic marker in other tumours. Nestin, a marker of immature endothelium, was previously applied in combination with Ki67 for proliferating endothelium as a novel marker (Nestin‐Ki67) of ongoing angiogenesis. Here, the prevalence and prognostic impact of vascular proliferation on lung cancer‐specific survival (LCSS) in lung adenocarcinomas was studied. Selected tumour slides from a cohort of 210 patients treated surgically for adenocarcinoma at Haukeland University Hospital (Norway) from 1993 to 2010 were stained for Nestin‐Ki67. VPI, the ratio between the density of proliferating vessels and the overall microvessel density were used, and the cut‐off value was set at 4.4% (upper quartile). High VPI was associated with the presence of blood vessel invasion (p = 0.007) and tumour necrosis (p = 0.007). Further, high VPI was significantly associated with reduced LCSS (p = 0.020). By multivariate analysis, VPI remained an independent prognostic factor for reduced LCSS (HR 1.7; 95% CI 1.04–2.68; p = 0.033) when adjusted for other prognostic clinico‐pathological features. In conclusion, microvessel proliferation assessed using the VPI was associated with aggressive tumour features such as blood vessel invasion and tumour necrosis and, independently, decreased LCSS. This marker should be further explored in separate cohorts, and in trials of anti‐angiogenesis therapy.

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Section: Discussionmentioning

confidence: 68%

Microvascular proliferation is associated with aggressive tumour features and reduced survival in lung adenocarcinoma

Ramnefjell

Aamelfot

Aziz

et al. 2017

The Journal of Pathology CR

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“…). Thus, the phenomena of vein wall vascularization with sprout formation from the intimal ECs, the polarized mode of migration (Bugyik et al, ), frequent mitoses, and initial microvessel expansion support a sprouting mechanism (Ausprunk and Folkman, ; Folkman and Shing, ; Díaz‐Flores et al, ; Ribatti and Crivellato, ). The participation of this type of angiogenesis is reinforced by the presence of mitoses in periendothelial cells of the growing vessels.…”

Section: Discussionmentioning

confidence: 99%

Piecemeal Mechanism Combining Sprouting and Intussusceptive Angiogenesis in Intravenous Papillary Formation Induced by PGE2 and Glycerol

Díaz‐Flores

Gutiérrez

García

et al. 2017

The Anatomical Record

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Recently, we demonstrated that in human intravascular papillary endothelial hyperplasia (IPEH), vein wall vascularization occurs in association with myriad papillae, a large part of which formed in the vascularized vein wall. Previously, using an animal model, we observed that PGE2 and glycerol administration around the femoral vein originates intense vascularization of the vein wall from its intimal endothelial cells (ECs). This vascularization is similar to that in IPEH. The aim of this study is to assess the mechanism of papillary formation, using this model after demonstrating papillary development in neo-vascularized femoral vein walls. In semithin and ultrathin sections, the sequential vascular and papillary development was as follows: (a) activation of vein intimal ECs, (b) sprouting of intimal ECs towards the vein media layer and microvessel development, (c) interconnection between neighboring microvessels originated elementary loops, which encircled vein wall components and formed papillae. The encircling ECs formed the papillary cover, and the encircled component formed the core. The papillae showed a similar structure to that of folds and pillars in intussusceptive angiogenesis, and (d) origin of secondary and complex loop systems by interconnection of neighboring elementary loops and by splitting of papillae by new loops, with abundant papillary development. In conclusion, the results support a piecemeal angiogenic mechanism in papillary formation, with association of sprouting and intussusceptive types of angiogenesis. Further studies are needed to assess whether the intravascular papillae described in several pathologic processes, including vessel tumors, such as Dabska's tumor, retiform hemangioendothelioma, and angiosarcoma, follow a similar mechanism. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1781-1792, 2017. © 2017 Wiley Periodicals, Inc.

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“…Based on active metabolism of tumor cells on continuous desire to oxygen and nutrient, they release and produce high amounts of proangiogenic factors that promote nourishing the vessel growth . These are some main positive regulator of angiogenesis, such as vascular endothelial growth factor (VEGF), fibroblast growth factor‐2 (FGF‐2), interleukin‐8 (IL‐8), placental growth factor (PlGF), transforming growth factor beta (TGFbeta), platelet derived growth factor (PDGF), angiopoietins (Angs), etc …”

Section: Introductionmentioning

confidence: 99%

Dopamine Delivery via pH‐Sensitive Nanoparticles for Tumor Blood Vessel Normalization and an Improved Effect of Cancer Chemotherapeutic Drugs

Taleb

Ding

Wang

et al. 2019

Adv Healthcare Materials

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Tumor blood vessels have been reported to be abnormal in both structure and function compared with those in normal tissues, leading to a hostile microenvironment and inadequate antitumor drug delivery. Dopamine, a chemical messenger, is proven to inhibit angiogenesis and improve tumor vessel normalization. Here, a mesoporous silicon nanoparticle (MSN) is constructed that is responsive to the weakly acidic pH of the tumor extracellular matrix for steady delivery and tumor‐localized release of dopamine. Then MSNs are functionalized with amine conjugated phenylboronicacid molecules, and dopamine is loaded by reacting with phenylboronic acid. In a weakly acidic environment, MSNs intelligently release dopamine due to the hydrolysis of boronic‐ester bond between dopamine and phenylboronic acid, resulting in an evident inhibition of vascular endothelial cell migration and tubule formation. It is shown that loading of dopamine into the functional MSNs significantly prolong the circulatory half‐life of this small molecule. After intravenous injection to tumor bearing mice, this nanoformulation induce tumor blood vessel normalization, thereby improving the antitumor chemotherapeutic efficacy of doxorubicin. This study demonstrates that the pH‐responsive MSN offers great potential for delivery of dopamine in vivo and the normalization of tumor vessels by dopamine can provide an auxiliary treatment for cancer chemotherapeutic drugs.

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Mechanisms of vascularization in murine models of primary and metastatic tumor growth

Cited by 36 publications

References 22 publications

Microvascular proliferation is associated with aggressive tumour features and reduced survival in lung adenocarcinoma

Microvascular proliferation is associated with aggressive tumour features and reduced survival in lung adenocarcinoma

Piecemeal Mechanism Combining Sprouting and Intussusceptive Angiogenesis in Intravenous Papillary Formation Induced by PGE2 and Glycerol

Dopamine Delivery via pH‐Sensitive Nanoparticles for Tumor Blood Vessel Normalization and an Improved Effect of Cancer Chemotherapeutic Drugs

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