Distribution of VEGF and flt-1 in the Normal Dog Tissues

Angiogenesis plays an essential role in the development of a neoplastic tumour by conditioning both its growth and the formation of metastases. The induction of blood vessel growth occurs under the influence of proangiogenic factors, among which Vascular Endothelial Growth Factor (VEGF) seems to be the most important. The aim of this research was to study the level of VEGF measured by ELISA in the serum of dogs with neoplasms of the oral cavity. The study material comprised samples of neoplastic tissue from 17 operated dogs and the serum of the examined animals as well as of dogs from the control group. The tissue samples were taken from dogs of different breeds, aged 6–14 years. The tumour type was determined in accordance with the applicable WHO classification. Blood samples taken from sick dogs and from animals of the control group were centrifuged, and immunoenzymatic labelling of VEGF was performed in the obtained serum using ELISA and R&D system reagents (Quantikine Canine VEGF). All stages of VEGF labelling were performed according to the recommendation of the test manufacturer. The median of VEGF in the serum of the dogs with neoplasms of the oral cavity was 40.64 pg/mL. The lowest value of 14.26 pg/mL was observed in the case of fibrosarcoma, and the highest value of 99.19 pg/mL in the case of squamous cell carcinoma. The VEGF median in the control group amounted to 11.14 pg/mL whereas the VEGF value in the groups of animals diagnosed with benign tumours ranged between 2.30 and 19.74 pg/mL. Elevated VEGF in the blood serum, in comparison with the benign tumour group and the control group, was observed in all examined neoplasms of the oral cavity. It was suggested that overexpression of VEGF can have a prognostic value and is useful in the early detection of neoplasms.

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“…The presence of VEGF receptors was also observed in healthy lung, skin and bladder tissue in dogs (Uchida et al, 2008).…”

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confidence: 74%

Elevated Vascular Endothelial Growth Factor (VEGF) levels in the blood serum of dogs with malignant neoplasms of the oral cavity

Sobczyńska-Rak

Polkowska

Silmanowicz

2014

Acta Veterinaria Hungarica

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“…VEGF-A, a strong angiogenic factor, is expressed at low levels in normal mammalian tissues; increased levels of VEGF-A were observed during ischemia or hypoxia, and in lesions characterized by angiogenesis. In a recent study [31], VEGF-A 120 , VEGF-A 164 , and VEGF-A 188 were detected in normal canine tissues, and VEGF-A 164 , which corresponds to human VEGF-A 165 , is the dominant molecular species. Canine VEGF-A 164 contains all the necessary information for the normal growth, remodeling, and patterning of blood vessels [32].…”

Section: Discussionmentioning

confidence: 99%

Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

et al. 2009

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BackgroundHuman hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes.MethodsSix primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets.ResultsHistopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors.ConclusionWe established 6 xenograft canine HSA tumors in nude mice and found that the expressions of angiogenic growth factors and their receptors in xenograft HSAs were similar to those in spontaneous HSA. Furthermore, we detected the expression of angiogenic homeobox genes; therefore, xenograft models may be useful in analyzing malignant growth in HSA.

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“…No studies have been published on the role of VEGF‐A in inflamed canine skin. One study reported the presence of VEGF isoforms and the receptor VEGFR‐1 in all tissues tested (liver, lungs, kidneys, heart, adrenal glands, thyroid, intestine, bladder, spleen and skin) in six healthy beagle dogs, with the highest concentrations in the lungs and heart . VEGF and its receptor were moderately to strongly evident in epidermis, sebaceous glands, apocrine glands, erector pili muscles and hair follicles .…”

Section: Discussionmentioning

confidence: 99%

Noninvasive evaluation of vascular endothelial growth factor‐A (VEGF‐A) protein concentrations in the stratum corneum and serum of healthy and atopic dogs

Cobiella

Gram

Santoro

2019

Veterinary Dermatology

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Background Vascular endothelial growth factor (VEGF) is a cytokine involved primarily in angiogenesis. In human atopic dermatitis (AD), VEGF has been detected in the stratum corneum and blood. Objective To evaluate VEGF‐A expression in the serum and stratum corneum of healthy and atopic dogs, and its possible correlation with disease severity in atopic dogs. Animal Fifteen atopic and 15 healthy, privately owned dogs. Methods and materials The severity of clinical signs associated with AD was evaluated with the Canine Atopic Dermatitis Extent and Severity Index (CADESI‐04). For all dogs, a single blood sample was performed and serum collected. Tape stripping (15 times) was performed on the left periocular area (lesional skin). A commercially available canine‐specific VEGF‐A enzyme‐linked immunosorbent assay was performed with all samples. Results Vascular endothelial growth factor‐A was undetectable in the serum. In the stratum corneum, there was no significant difference in VEGF‐A concentrations between healthy (mean 89.4 ± 59.5 pg/ml) and atopic dogs (mean 100.3 ± 77.1pg/ml) (P = 0.71). There was no correlation between stratum corneum VEGF‐A concentrations and CADESI‐04 scores. Conclusions and clinical importance The role of VEGF in canine AD is unclear. Because of many variants, VEGF‐C and VEGF‐D or VEGF‐A isotopes should be explored in the skin to better evaluate the role of VEGF in canine atopy. Full‐thickness skin biopsy, molecular biology and histopathological investigation may be necessary to further assess cutaneous VEGF expression.

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Distribution of VEGF and flt-1 in the Normal Dog Tissues

Cited by 17 publications

References 12 publications

Elevated Vascular Endothelial Growth Factor (VEGF) levels in the blood serum of dogs with malignant neoplasms of the oral cavity

Elevated Vascular Endothelial Growth Factor (VEGF) levels in the blood serum of dogs with malignant neoplasms of the oral cavity

Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

Noninvasive evaluation of vascular endothelial growth factor‐A (VEGF‐A) protein concentrations in the stratum corneum and serum of healthy and atopic dogs

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