Abstract
Recent studies have provided evidence that the secretory cells of the fallopian tube (oviduct) are a probable origin for high-grade serous ovarian carcinoma. In addition to secretory cells, the fallopian tube epithelium consists of ciliated cells and CD44+ undifferentiated stem-like cells. Loss of PAX2 expression is recognized as an early event in epithelial transformation, but the specific role of PAX2 in this transition is unknown. The aim of this study was to define the role of PAX2 in oviductal epithelial (OVE) cells and its response to transforming growth factor β1 (TGFβ), characterizing specifically its potential involvement in regulating stem cell-like behaviors that may contribute to formation of cancer-initiating cells. Treatment of primary cultures of mouse OVE cells with TGFβ induced an epithelial-mesenchymal transition (EMT) associated with decreased expression of PAX2 and an increase in the fraction of cells expressing CD44. PAX2 knockdown in OVE cells and overexpression in ovarian epithelial cells confirmed that PAX2 inhibits stem cell characteristics and regulates the degree of epithelial differentiation of OVE cells. These results suggest that loss of PAX2, as occurs in serous tubal intraepithelial carcinomas, may shift secretory cells to a more mesenchymal phenotype associated with stem-like features.
Highlights
For more than 30 years, scientists focused on ovarian surface epithelial (OSE) cells and inclusion cysts derived from them as the origin of ovarian carcinomas [1, 2]
The aim of this study was to define the role of PAX2 in oviductal epithelial (OVE) cells and its response to transforming growth factor β1 (TGFβ), characterizing its potential involvement in regulating stem cell-like behaviors that may contribute to formation of cancer-initiating cells
Recent studies have provided evidence that fallopian tube epithelial cells are a probable cell of origin for many high-grade serous cancers [5,6,7,8], with precursor lesions frequently detected in the distal end of the fallopian tube in patients with a high risk for ovarian cancer [9]
Summary
For more than 30 years, scientists focused on ovarian surface epithelial (OSE) cells and inclusion cysts derived from them as the origin of ovarian carcinomas [1, 2]. Recent studies have provided evidence that fallopian tube epithelial cells are a probable cell of origin for many high-grade serous cancers [5,6,7,8], with precursor lesions frequently detected in the distal end (fimbria) of the fallopian tube in patients with a high risk for ovarian cancer [9]. Crum et al have proposed a model to explain tumor progression from serous tubal intraepithelial carcinoma (STIC) to invasive carcinoma [10, 11], implicating secretory cell outgrowths (SCOUTs) as potential early precursor lesions. SCOUTs show frequent loss of paired box protein 2 (PAX2) expression and often acquire P53 expression [12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
