Abstract
Abstract Thyroid is amongst one of the most vascularized tissues of the human body and studies have demonstrated that neo-vascularization is critical for growth and metastasis of thyroid carcinoma with well differentiated thyroid carcinoma metastasizing to the lymph nodes of the neck in 50% of the patients. The perceived risk of thyroid proliferative diseases in women is one in eight, a risk similar to that of breast cancer, suggesting a possible role of female reproductive hormones such as estrogen in this epidemiological distribution. The identification of systemic modulators such as estrogen and markers of metastatic phenotype or neo-vascularization in thyroid cancer is a clinical need. We developed an in vitro thyroid cell culture model to study the effect of estrogen on metastatic phenotype of thyroid cells. We discovered that estradiol modulates metastatic properties of these thyroid cells as evidenced by an increase in in vitro migration, invasion and adhesion in presence of estradiol which correlates with a concomitant downregution of tumor suppressive protein, β-catenin. Restitution of cadherin/catenin complex by fulvestrant suppresses the metastatic phenotype of thyroid cells thus validating our findings of β-catenin as a significant metastatic phenotype marker. Furthermore, we developed an in vivo animal model so as to study the effect of estrogen on neo-vasculature in thyroid cancer. We found that estradiol acts as a mobilizing agent for bone marrow derived endothelial progenitor cells (BM-EPCs) resulting in homing of enhanced numbers of BM-EPCs to orthotopic tumor when ovariectomized mice were supplemented with estradiol pellets. We also discovered that thyroid cells secrete paracrine factors which results in enhanced migration of BM-EPCs as evidenced by in vitro experimental model suggesting that mobilization of BM-EPCs is tumor responsive. In conclusion, our data provides strong evidence that estradiol enhances the metastatic propensity of thyroid cells and mobilizes BM-EPCs to the thyroid tumor. These findings will allow for the possible development of anti-estrogenic compounds that target catenin mediated metastasis and/or stem cells mediated neo-vascularization of thyroid cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 420.
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