Vascular Endothelial Growth Factor – Marker for Proliferation in Thyroid Diseases?

Abstract

Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis and is involved in tumor development. To date, the role of VEGF in benign diseases of the thyroid is not well known. The purpose of the present study is to determine the expression of VEGF and its receptors in primary cultures of human thyrocytes. Methods: 50 patients with uninodular (n=11), multinodular (n=15), recurrent goiter (n=14) and Graves? disease (n=10) were enrolled. Nodular and corresponding paranodular tissue was obtained after surgery and investigated. RNA and protein were extracted from primary thyrocyte cultures. PCR, western blot and ELISA were performed to evaluate VEGF isoforms and VEGF receptor 1 and 2. Results: Significantly increased transcription and protein expression of VEGF and its receptors were detected in nodular tissue of uninodular and recurrent goiter compared to the corresponding normal tissue. Active secretion of VEGF by thyrocytes was confirmed by ELISA. In multinodu?lar goiter, no difference could be found between nodular and corresponding paranodular tissue in terms of expression of VEGF or its receptors. Furthermore, we found the highest levels of VEGF and its receptors in tissue obtained from patients with Graves? disease. Conclusion: Increased expression of VEGF and its receptors might be crucial in the proliferation of thyrocytes and therefore may contribute to the development of goiter and goiter recurrence.

Transformujący czynnik wzrostu β1 (TGFβ1) i naczyniowo-śródbłonkowy czynnik wzrostu (VEGF) we krwi ludzi zdrowych i chorych z orbitopatią Gravesa — nowy mechanizm działania glikokortykosteroidów?

“…Endocrine glands are well vascularised and the structure of their vessels (fenestration of epithelium) facilitates the exchange of various substances, including hormones. The amount of VEGF in the thyroid gland is greater in the frequently occurring parenchymal and nodular goitres compared to healthy subjects, although a difference between the pathological tissues is not stated [25,33,56]. Increased mRNA and protein expression of VEGF and its receptors detected in nodular tissue of uninodular and recurrent goitre compared to the corresponding normal tissue might be crucial in the proliferation of thyrocytes, and therefore may contribute to the development of goitre and goitre recurrence [56].…”

“…The amount of VEGF in the thyroid gland is greater in the frequently occurring parenchymal and nodular goitres compared to healthy subjects, although a difference between the pathological tissues is not stated [25,33,56]. Increased mRNA and protein expression of VEGF and its receptors detected in nodular tissue of uninodular and recurrent goitre compared to the corresponding normal tissue might be crucial in the proliferation of thyrocytes, and therefore may contribute to the development of goitre and goitre recurrence [56]. Tissues of lymphocytic thyroiditis and differentiated thyroid carcinomas have a stronger expression of VEGF than healthy gland tissues [25,57,58].…”

“…In people with Graves' disease, VEGF mRNA has been found to be localised in the hyperplastic thyroid follicular cells, and mRNA and protein of Flt-1 in the endothelial cells of all thyroid tissues [61]. The highest expression of VEGF and its receptors has been found in tissue obtained from patients with Graves' disease [56]. It has been found that serum VEGF levels are elevated in patients with untreated Graves' disease and Hashimoto's disease, and correlate positively with the degree of thyroid vascularity assessed by colour Doppler ultrasound.…”

Molecular Pathways Associated with Aggressiveness of Papillary Thyroid Cancer

“…High expression of VEGF in TC seems to correlate with an increased risk of recurrence, lymph node metastases, and advanced tumor stage [66]. Neuropilin-2 is a coreceptor for VEGF-D and correlates with lymph node metastases in PTC [67].…”

Age-associated functional morphology of thyroid and its impact on the expression of vimentin, cytokeratins and VEGF. The role of nigella in refinement

“…It has been suggested that VEGF and its receptors are present in the thyroid epithelial cells and they contribute to the regulation of the development and function of thyrocytes [15,16]. Increased expression of VEGF and its receptors might be crucial in the regulation of the proliferation of thyroid epithelial cells [15].…”