Abstract
The cause of death among the majority of endometrial cancer patients involves migration of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into neighbouring organs. It is, thereby, important to identify factors that mediate metastasis. Cell adhesion and migration are modified by the mesenchymal stem cell (MSC) marker Sushi domain containing 2 (SUSD2), a type I transmembrane protein that participates in the orchestration of cell adhesion and migration through interaction with its partner Galactosidase-binding soluble-1 (LGALS1). MSCs have emerged as attractive targets in cancer therapy. Human endometrial adenocarcinoma (Ishikawa) cells were treated with TGFβ (10 ng/ml) for 72h. SUSD2, LGALS1 and MKI67 transcript levels were quantified using qRT-PCR. The proportion of SUSD2 positive (SUSD2+) cells and SMAD2/3 abundance were quantified by FACS and Western blotting, respectively. Senescent cells were identified with β-galactosidase staining; cell cycle and cell death were quantified using Propidium Iodide staining. Treatment of endometrial cancer cells (Ishikawa cells) with TGFβ (10 ng/ml) significantly decreased SUSD2 transcript levels and the proportion of SUSD2 positive cells. Silencing of SUSD2 using siRNA resulted in senescence and cell death of Ishikawa cells via activation of SMAD2/3. These findings suggest that SUSD2 counteracts senescence and cell death and is thus a potential chemotherapeutic target in human endometrial cancer.
Highlights
Endometrial cancer is the most common gynaecological malignancy, the incidence of which is increasing worldwide [1]
The present study addressed the effect of TGFβ on mesenchymal stem cell (MSC) marker Sushi domain containing 2 (SUSD2) in Ishikawa cells, a well differentiated endometrial adenocarcinoma cell line
At concentrations ranging from 10–50 ng/ml, TGFβ further reduced the percentage of SUSD2+ cells
Summary
Endometrial cancer is the most common gynaecological malignancy, the incidence of which is increasing worldwide [1]. Endometrial cancers are often classified into two general clinicopathological types. Type I endometrial tumors, which account for ~70% of endometrial. SUSD2 downregulation causes senescence and death of endometrial tumor cells cancers, are primarily comprised of low-grade endometrioid tumors and are associated with favorable prognosis. Type II endometrial cancers comprise a group of high-risk tumors of serous, clear cell or high-grade endometrioid histology that are highly invasive and associated with poor survival [2]. 75% of all endometrial cancer related deaths can be attributed to the aggressive behaviour of these high-risk tumours [2]. Investigations on the molecular mechanisms contributing to endometrial cancer metastasis could lead to the development of improved therapeutic strategies
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: 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.