Three-dimensional modeling of the human fallopian tube fimbriae
| Autor: | Rajul Kothari, Suzanne M. Quartuccio, Sharon L. Eddie, Jessica A. Shepherd, Joanna E. Burdette, Jie Zhu, J. Julie Kim, Teresa K. Woodruff |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Anatomic Pathology medicine.medical_specialty animal structures media_common.quotation_subject Fimbria Biology medicine.disease_cause Article Tissue Culture Techniques In vivo medicine Humans Ovulation Fallopian Tubes Cell Proliferation media_common Ovarian Neoplasms Obstetrics and Gynecology Epithelial Cells medicine.disease female genital diseases and pregnancy complications Serous fluid medicine.anatomical_structure Oncology Cancer research Female Carcinogenesis Ovarian cancer Ex vivo Fallopian tube |
| Zdroj: | Gynecologic Oncology. 136:348-354 |
| ISSN: | 0090-8258 |
| DOI: | 10.1016/j.ygyno.2014.12.015 |
| Popis: | Objective Ovarian cancer is the most lethal gynecological malignancy that affects women. Recent data suggests that the disease may originate in the fallopian fimbriae; however, the anatomical origin of ovarian carcinogenesis remains unclear. This is largely driven by our lack of knowledge regarding the structure and function of normal fimbriae and the relative paucity of models that accurately recapitulate the in vivo fallopian tube. Therefore, a human three-dimensional (3D) culture system was developed to examine the role of the fallopian fimbriae in serous tumorigenesis. Methods Alginate matrix was utilized to support human fallopian fimbriae ex vivo . Fimbriae were cultured with factors hypothesized to contribute to carcinogenesis, namely; H 2 O 2 (1mM) a mimetic of oxidative stress, insulin (5μg/ml) to stimulate glycolysis, and estradiol (E 2 , 10nM) which peaks before ovulation. Cultures were evaluated for changes in proliferation and p53 expression, criteria utilized to identify potential precursor lesions. Further, secretory factors were assessed after treatment with E 2 to identify if steroid signaling induces a pro-tumorigenic microenvironment. Results 3D fimbriae cultures maintained normal tissue architecture up to 7days, retaining both epithelial subtypes. Treatment of cultures with H 2 O 2 or insulin significantly induced proliferation. However, p53 stabilization was unaffected by any particular treatment, although it was induced by ex vivo culturing. Moreover, E 2 -alone treatment significantly induced its canonical target PR and expression of IL8, a factor linked to poor outcome. Conclusions 3D alginate cultures of human fallopian fimbriae provide an important microphysiological model, which can be further utilized to investigate serous tumorigenesis originating from the fallopian tube. |
| Databáze: | OpenAIRE |
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