title: Estrogen and thyroid cancer is a stem affair: A preliminary study.
abstract: Gender influences Papillary Thyroid Cancer (PTC) with an incidence of 3:1 when comparing women to men with different aggressiveness. This gender discrepancy suggests some role of sex hormones in favoring the malignant progression of thyroid tissue to cancer. Estrogens are known to promote Stem Cell self-renewal and, therefore, may be involved in tumor initiation. The goals of these studies are to investigate the underlying causes of gender differences in PTC by studying the specific role of estrogens on tumor cells and their involvement within the Cancer Stem Cell (CSC) compartment. Exposure to 1nmoll-1Estradiol for 24h promotes growth and maintenance of PTC Stem Cells, while inducing dose-dependent cellular proliferation and differentiation following Estradiol administration. Whereas mimicking a condition of hormonal imbalance led to an opposite phenotype compared to a continuous treatment. In vivo we find that Estradiol promotes motility and tumorigenicity of CSCs. Estradiol-treated mice inoculated with Thyroid Cancer Stem Cell-enriched cells developed larger tumor masses than control mice. Furthermore, Estradiol-pretreated Cancer Stem cells migrated to distant organs, while untreated cells remained circumscribed. We also find that the biological response elicited by estrogens on Papillary Thyroid Cancer in women differed from men in pathways mediated. This could explain the gender imbalance in tumor incidence and development and could be useful to develop gender specific treatment of (PTC).
authors.affiliation: Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padova, Padova, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Zane
authors.affiliation: Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padova, Padova, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Parello
authors.affiliation: Surgical Pathology and Cytopathology Unit, Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Pennelli
authors.affiliation: Department of Drug Discovery and Pharmaceutical Sciences, Medical University of South Carolina, USA.
authors.forename: Danyelle M
authors.initials: DM
authors.lastname: Townsend
authors.affiliation: Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padova, Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Merigliano
authors.affiliation: Endocrinology, Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Boscaro
authors.affiliation: Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padova, Padova, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Toniato
authors.affiliation: Internal Medicine Unit, Department of Molecular Medicine, University of Padua, Padova, Italy.
authors.forename: Giovannella
authors.initials: G
authors.lastname: Baggio
authors.affiliation: Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padova, Padova, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Pelizzo
authors.affiliation: Santa Maria della Misericordia Hospital, Rovigo, Italy. Electronic address: Domenico.rubello@libero.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
authors.affiliation: Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padova, Padova, Italy.
authors.forename: Isabella Merante
authors.initials: IM
authors.lastname: Boschin
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004967:Estrogens / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009374:Neoplasms, Experimental; D012727:Sex Characteristics; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013964:Thyroid Neoplasms / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004967:Estrogens
keywords: Cancer signaling; Cancer stem cells; Estrogen; Gender medicine; Thyroid cancer