Correlation between the expression of vegf and survival in osteosarcoma

Baptista, André Mathias; Camargo, André Ferrari de França; Filippi, Renée Zon; Oliveira, Cláudia Regina Gomes Cardim Mendes de; Neto, Raymundo Soares de Azevedo; Camargo, Olavo Pires de

doi:10.1590/1413-78522014220500978

Cited by 15 publications

(7 citation statements)

References 20 publications

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“…For example, study of VEGF secretion using mice models have suggested a strong relationship between VEGF and tumor aggressiveness [ 65 ]. In addition, two independent studies compared VEGF secretion and non-metastatic osteosarcoma proliferation by clinical observation on patients, and suggested that poor prognosis and high local recurrences can be associated with boosted VEGF secretion [ 86 , 87 ]. The approach developed in this study can also help to systematically analyze the autocrine activities of cytokines in tumors by replicating the conditions which lead to malignancy in vivo .…”

Section: Discussionmentioning

confidence: 99%

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

2020

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Vascular endothelial growth factor (VEGF) is a major cytokine in tumor biology affecting tumor survival, aggressiveness and pro-angiogenetic activities. In addition, cellular stresses often result in aggressive pro-angiogenetic behavior in tumors. For in vitro study, conventional monolayer cell culture has been broadly exploited; however, it often provides limited information due to its different microenvironment from that in vivo. Recently, three-dimensional (3D) cell spheroid culture provides in vivo-like microenvironments to study tumor biology and their survival mechanisms with better predictive power. In this work, vascular endothelial growth factor of type A (VEGF-A) secretion from osteosarcoma (MG-63) cells cultured using monolayer and 3D spheroid models under two stress conditions: nutrient deficiency (reduced serum culture) and hypoxia-inducible factor (HIF) inhibition (HIF inhibitor, YC-1) are characterized and systematically compared. In order to obtain ample sample size for consistent characterization of cellular responses from cancer spheroids under the stresses and compare the responses to those from the conventional monolayer model, a microfluidic spheroid formation and culture device is utilized in the experiments. In the analysis, cell viability is estimated from captured images, and quantification of VEGF-A secreted from the cells is achieved using enzyme-linked immunosorbent assay (ELISA). The experimental results show that the viabilities decrease when the cells face higher stress levels in both monolayer and 3D spheroid culture models; however, the VEGF-A secretion profiles between the cell culture models are different. The VEGF-A secretion decreases when the cells face higher stress conditions in the monolayer cell culture. In contrast, for the 3D spheroid culture, the VEGF-A concentration decreases for low stress levels but increases while the stress level is high. The VEGF-A regulation in the 3D models mimics in vivo cases of tumor survival and can provide insightful information to investigate tumor angiogenesis in vitro. The approach developed in this paper provides an efficient method to quantitatively and statistically study tumor growth kinetics and stress responses from highly uniform samples and it can also be applied to compare the underlying biomolecular mechanisms in monolayer and 3D spheroid culture models to elucidate the effects of microenvironments on cellular response in cancer research.

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Section: Discussionmentioning

confidence: 99%

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

2020

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“…Advanced Os is considered incurable and has a very poor response to conventional cytotoxic chemotherapy, which is mainly based on methotrexate and doxorubicin [17]. Better understanding of the biology of Os might support the design of new therapeutic strategies, including anti-angiogenic drugs.…”

Section: Discussionmentioning

confidence: 99%

The early stages of tumor angiogenesis in human osteosarcoma: a nude mice xenotransplant model

et al. 2015

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Osteosarcoma (Os) is the most common malignant bone tumor in childhood and not rare in adults. In recent years, much research has focused on the role of angiogenesis in tumor development, growth, invasion, and metastasis. The aims of this study were to characterize neovascularization established between the xenotransplanted Os and the host at histological, immunohistochemical, ultrastructural, and molecular level, and to evaluate if this model could be used in testing new anti-angiogenic drugs. Three xenotransplanted human Os were evaluated. Tumor pieces 3-4 mm in size were implanted subcutaneously on the back of athymic Balb-c nude mice (n = 14). The animals were killed at 24, 48, and 72 h and 7, 14, 21, and 28 days after implantation. Tumor samples were either fixed in 10 % formaldehyde and embedded in paraffin for histological analysis, or fixed with glutaraldehyde (2 %) for electron microscopy or retained non-fixed for molecular analysis (ELISA and qRT-PCR). Morphologically, intense neo-vasculogenesis within tumor parenchyma was present between the first and third week after transplantation. Immunohistochemistry demonstrated overexpression of VEGF and their receptors together with PDFGFRA 24-48 h after tumor implantation. Additionally, neoplastic cells co-expressed chemokines (CXCL9, CXCL10, and GRO) and their receptors. Molecular studies showed two expression profiles, distinguishing an early and a late phase in the angiogenic process. In Os, our model showed two stages of induced angiogenesis, with close association between histological and molecular events. This approximation could be of use for testing the effect of different anti-angiogenic agents.

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“…After assessing the entire text of the remaining 32 studies, 10 articles were excluded for insufficient data. Finally, 22 studies with a total of 1144 osteosarcoma patients were included in this study [ 10 , 11 , 18 – 37 ]. The detailed flowchart of the study filtrating process is shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To clarify the mechanism of VEGF in the advancement of osteosarcoma, the association between VEGF and prognosis features of osteosarcoma has been assessed. However, the prognostic and clinicopathological value of VEGF remains controversial [ 10 , 11 ]. Previous relevant meta-analyses have been performed to define the clinical significance of VEGF expression in osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

The role of vascular endothelial growth factor as a prognostic and clinicopathological marker in osteosarcoma: a systematic review and meta-analysis

et al. 2021

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Background In recent years, numerous investigations have been conducted to determine the clinical significance and critical functions of vascular endothelial growth factor (VEGF) in various malignant cancers. The purpose of this meta-analysis was to comprehensively evaluate the prognostic and clinicopathological value of VEGF in patients with osteosarcoma. Methods We performed a systematic literature retrieval of available databases. Odds ratios (ORs) or standard mean difference (SMD) for clinicopathological parameters, hazard ratios (HRs) for overall survival and disease-free survival were calculated to assess the correlation between VEGF expression and prognosis in patients with osteosarcoma. Results A total of 22 studies with 1144 patients were included in our study. Pooled analyses showed that VEGF overexpression predicted worse overall survival (HR, 2.42; 95% CI, 1.87–3.11, p < 0.001) and disease-free survival (HR, 2.604; 95% CI, 1.698–3.995, p < 0.001), respectively. Furthermore, investigation regarding osteosarcoma clinicopathologic characteristics suggested that high VEGF expression was significantly associated with metastasis (OR, 4.39; 95% CI, 2.77–6.95; p < 0.001), clinical stage (OR, 0.73; 95% CI, 0.62–0.87; p < 0.001), and microvessel density (SMD, 3.33, 95% CI,1.57–5.10, p < 0.001), but not associated with tumor location, gender, age, local recurrence, and chemotherapy response. Conclusion Our meta-analysis findings suggest that elevated VEGF expression may be a predictive biomarker for poor prognosis and adverse clinicopathological characteristics in patients with osteosarcoma.

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Correlation between the expression of vegf and survival in osteosarcoma

Cited by 15 publications

References 20 publications

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

The early stages of tumor angiogenesis in human osteosarcoma: a nude mice xenotransplant model

The role of vascular endothelial growth factor as a prognostic and clinicopathological marker in osteosarcoma: a systematic review and meta-analysis

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