Estrogen-Mediated Angiogenesis in Thyroid Tumor Microenvironment Is Mediated Through VEGF Signaling Pathways

Kamat, Ameet; Rajoria, Shilpi; George, Andrea L.; Suriano, Robert; Shanmugam, Arul; Megwalu, Uchechukwu C.; Prakash, Pradeep Bangalore; Tiwari, Raj K.; Schantz, Stimson P.

doi:10.1001/archoto.2011.194

Cited by 32 publications

(24 citation statements)

References 14 publications

(26 reference statements)

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“…Additionally, estrogen stimulation may lead to an increased metastatic phenotype (55), possibly through induction of matrix metalloproteinase activity (56). Furthermore, in cell lines, estrogen may promote thyroid cancer cell migration and invasion and angiogenesis through vascular endothelial growth factor pathways (57). …”

Section: Resultsmentioning

confidence: 99%

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: The Increasing Incidence of Thyroid Cancer

et al. 2015

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Objective (1) Describe current epidemiology of thyroid cancer in the United States; (2) evaluate hypothesized causes of the increased incidence of thyroid cancer; and (3) suggest next steps in research and clinical action. Methods Analysis of data from Surveillance, Epidemiology and End Results System and the National Center for Vital Statistics. Literature review of published English-language articles through December 31, 2013. Results The incidence of thyroid cancer has tripled over the past 30 years, whereas mortality is stable. The increase is mainly comprised of smaller tumors. These facts together suggest the major reason for the increased incidence is detection of subclinical, nonlethal disease. This has likely occurred through: health care system access, incidental detection on imaging, more frequent biopsy, greater volumes of and extent of surgery, and changes in pathology practices. Because larger-size tumors have increased in incidence also, it is possible that there is a concomitant true rise in thyroid cancer incidence. The only clearly identifiable contributor is radiation exposure, which has likely resulted in a few additional cases annually. The contribution of the following causes to the increasing incidence is unclear: iodine excess or insufficiency, diabetes and obesity, and molecular disruptions. The following mechanisms do not currently have strong evidence to support a link with the development of thyroid cancer: estrogen, dietary nitrate, and autoimmune thyroid disease. Conclusion Research should focus on illuminating which thyroid cancers need treatment. Patients should be advised of the benefits as well as harms that can occur with treatment of incidentally identified, small, asymptomatic thyroid cancers.

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Section: Resultsmentioning

confidence: 99%

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: The Increasing Incidence of Thyroid Cancer

et al. 2015

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“…In this study, we found that both the positive percentage and total score of VEGF expression were significantly decreased in female PTC patients of reproductive age with exclusively nuclear ERβ1 expression as compared with those with extranuclear localization of ERβ1, suggesting that estrogen may suppress VEGF expression through genomic actions mediated by ERβ1 localized to the nuclei of PTC cells. It has been reported that a follicular thyroid cancer cell line, ML-1, secreted more VEGF after estrogen stimulation, likely as a result of ER signaling [9]. In an animal model of ischemic stroke, ERβ contributed to the reduction of vasogenic edema via the inhibition of VEGF production [58].…”

Section: Discussionmentioning

confidence: 99%

Differential expression patterns and clinical significance of estrogen receptor-α and β in papillary thyroid carcinoma

Huang

Dong

et al. 2014

BMC Cancer

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BackgroundThe incidence of papillary thyroid cancer (PTC) is markedly higher in women than men during the reproductive years. In vitro studies have suggested that estrogen may play an important role in the development and progression of PTC through estrogen receptors (ERs). This study aimed to investigate the expression patterns of the two main ER subtypes, α and β1 (wild-type ERβ), in PTC tissue and their clinical significance.MethodsImmunohistochemical staining of thyroid tissue sections was performed to detect ER expression in female patients with PTC (n = 89) and nodular thyroid goiter (NTG; n = 30) using the Elivision™ plus two-step system. The relationships between ER subtype expression and clinicopathological/biological factors were further analyzed.ResultsThe positive percentage and expression levels of ERα were significantly higher in female PTC patients of reproductive age (18–45 years old; n = 50) than age-matched female NTG patients (n = 30), while ERβ1 exhibited the opposite pattern. There was no difference in ERα or ERβ1 expression between female PTC patients of reproductive age and those of advanced reproductive age (>45 years old; n = 39). In the female PTC patients of reproductive age, ERα expression level was positively correlated with that of Ki-67, while ERβ1 was negatively correlated with mutant P53. Furthermore, more patients with exclusively nuclear ERα expression had extrathyroidal extension (ETE) as compared with those with extranuclear ERα localization. VEGF expression was significantly decreased in female PTC patients of reproductive age with only nuclear ERβ1 expression when compared with those with extranuclear ERβ1 localization. In PTC patients of advanced reproductive age, neither ERα nor ERβ1 expression showed any correlation with that of Ki-67, mutant P53, VEGF, tumor size, TNM stage, ETE, or lymph node metastases.ConclusionsThe differential expression patterns of the two ER subtypes between PTC and NTG indicate that ERα may be a useful immunohistochemical marker for differential diagnosis of PTC. The associations of ER subtype expression with Ki-67, mutant P53, VEGF expression and ETE in female PTC patients of reproductive age suggest that estrogen-activated ERα may mediate stimulatory effects on PTC growth and progression whereas ERβ1 has some inhibitory actions.

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“…VEGF has the capacity to induce angiogenesis by detachment of quiescent endothelial cells from their parental vessels followed by migration of the cells into the neighboring stroma (Krock et al 2011). In vitro thyroid cancer cells secreted VEGF in response to estrogen treatment (Kamat et al 2011). Incubation of human umbilical vein endothelial cells with a conditioned medium from estrogen-treated cancer cells resulted in angiogenesis-associated events such as tubulogenesis and migration.…”

Section: Estrogen and Angiogenesis In Thyroid Cancermentioning

confidence: 99%

Estrogen and its role in thyroid cancer

Derwahl¹,

Nicula²

2014

Endocrine Related Cancer

227

166

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Proliferative thyroid diseases are more prevalent in females than in males. Upon the onset of puberty, the incidence of thyroid cancer increases in females only and declines again after menopause. Estrogen is a potent growth factor both for benign and malignant thyroid cells that may explain the sex difference in the prevalence of thyroid nodules and thyroid cancer. It exerts its growth-promoting effect through a classical genomic and a non-genomic pathway, mediated via a membrane-bound estrogen receptor. This receptor is linked to the tyrosine kinase signaling pathways MAPK and PI3K. In papillary thyroid carcinomas, these pathways may be activated either by a chromosomal rearrangement of the tyrosine receptor kinase TRKA, by RET/PTC genes, or by a BRAF mutation and, in addition, in females they may be stimulated by high levels of estrogen. Furthermore, estrogen is involved in the regulation of angiogenesis and metastasis that are critical for the outcome of thyroid cancer. In contrast to other carcinomas, however, detailed knowledge on this regulation is still missing for thyroid cancer.

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Estrogen-Mediated Angiogenesis in Thyroid Tumor Microenvironment Is Mediated Through VEGF Signaling Pathways

Cited by 32 publications

References 14 publications

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: The Increasing Incidence of Thyroid Cancer

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: The Increasing Incidence of Thyroid Cancer

Differential expression patterns and clinical significance of estrogen receptor-α and β in papillary thyroid carcinoma

Estrogen and its role in thyroid cancer

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