scholarly journals Hypoxia Regulates DPP4 Expression, Proteolytic Inactivation, and Shedding from Ovarian Cancer Cells

2020 ◽  
Vol 21 (21) ◽  
pp. 8110 ◽  
Author(s):  
Laura R. Moffitt ◽  
Maree Bilandzic ◽  
Amy L. Wilson ◽  
Yiqian Chen ◽  
Mark D. Gorrell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Specific Activity ◽  
Tissue Type ◽  
Ovarian Cancer Cells ◽  
Dipeptidyl Peptidase 4 ◽  
Hypoxic Conditions ◽  
Dependent Inactivation ◽  
Functional Consequences ◽  
Proteolytic Shedding

The treatment of ovarian cancer has not significantly changed in decades and it remains one of the most lethal malignancies in women. The serine protease dipeptidyl peptidase 4 (DPP4) plays key roles in metabolism and immunity, and its expression has been associated with either pro- or anti-tumour effects in multiple tumour types. In this study, we provide the first evidence that DPP4 expression and enzyme activity are uncoupled under hypoxic conditions in ovarian cancer cells. Whilst we identified strong up-regulation of DPP4 mRNA expression under hypoxic growth, the specific activity of secreted DPP4 was paradoxically decreased. Further investigation revealed matrix metalloproteinases (MMP)-dependent inactivation and proteolytic shedding of DPP4 from the cell surface, mediated by at least MMP10 and MMP13. This is the first report of uncoupled DPP4 expression and activity in ovarian cancer cells, and suggests a previously unrecognized, cell- and tissue-type-dependent mechanism for the regulation of DPP4 in solid tumours. Further studies are necessary to identify the functional consequences of DPP4 processing and its potential prognostic or therapeutic value.

scholarly journals Sitagliptin Modulates the Response of Ovarian Cancer Cells to Chemotherapeutic Agents

2020 ◽  
Vol 21 (23) ◽  
pp. 8976
Author(s):  
Agnieszka Kosowska ◽  
Wojciech Garczorz ◽  
Agnieszka Kłych-Ratuszny ◽  
Mohammad Reza F. Aghdam ◽  
Małgorzata Kimsa-Furdzik ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Strong Association ◽  
Chemotherapeutic Agents ◽  
Ovarian Cancer Cells ◽  
Cytostatic Drug ◽  
Dipeptidyl Peptidase 4 ◽  
Response To Chemotherapy ◽  
Induced Apoptosis

The strong association between diabetes mellitus type 2 and cancer is observed. The incidence of both diseases is increasing globally due to the interaction between them. Recent studies suggest that there is also an association between cancer incidence and anti-diabetic medications. An inhibitor of dipeptidyl-peptidase 4 (DPP-4), sitagliptin, is used in diabetes treatment. We examined the influence of sitagliptin alone or in combination with a cytostatic drug (paclitaxel) on the development of epithelial ovarian cancer cells and the process of metastasis. We examined migration, invasiveness, apoptosis, and metalloproteinases (MMPs) and their inhibitors’ (TIMPs) production in two human ovarian cancer cell lines. Sitagliptin induced apoptosis by caspase 3/7 activation in paclitaxel-treated SKOV-3 and OVCAR-3 cells. Sitagliptin maintained paclitaxel influence on ERK and Akt signaling pathways. Sitagliptin additionally reduced migration and invasiveness of SKOV-3 cells. There were distinct differences of metalloproteinases production in sitagliptin-stimulated ovarian cancer cells in both cell lines, despite their identical histological classification. Only the SKOV-3 cell line expressed MMPs and TIMPs. SKOV-3 cells co-treated with sitagliptin and paclitaxel decreased concentrations of MMP-1, MMP-2, MMP-7, MMP-10, TIMP-1, TIMP-2. The obtained data showed that sitagliptin used with paclitaxel may be considered as a possibility of pharmacological modulation of intracellular transmission pathways to improve the response to chemotherapy.

scholarly journals Hypoxia-Induced LncRNA-MIR210HG Promotes Cancer Progression By Inhibiting HIF-1α Degradation in Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Ping Liu ◽  
Huiqiong Huang ◽  
Xiaorong Qi ◽  
Ce Bian ◽  
Meng Cheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Hypoxic Conditions ◽  
Qpcr Analysis ◽  
And Function

LncRNA-MIR210HG plays crucial roles in the progression of diverse cancers. However, the expression and function of MIR210HG in ovarian cancer remains unclear. In the present study, we aimed to determine the expression and function of lncRNA-MIR210HG in ovarian cancer under hypoxic conditions. MIR210HG expression in ovarian cancer cells under hypoxic conditions was determined by qPCR analysis, and the distribution was determined by FISH and qPCR analysis based on cell nucleus and cytosol RNA extraction. Epithelial-Mesenchymal Transition (EMT) assay and human umbilical vein endothelial cell-based tube formation and migration assays were employed to determine the potential function of MIR210HG in vitro, followed by establishment of a subcutaneous tumor model in mice. The direct target of MIR210HG was determined by RNA pull-down and western blotting. Furthermore, the expression and clinical correlation of MIR210HG was determined based on malignant tissues from ovarian cancer patients. Our results indicated that MIR210HG was induced by hypoxia, which is HIF-1α dependent and mainly located in the cytosol of ovarian cancer cells. Knockdown of MIR210HG significantly inhibited EMT and tumor angiogenesis in vitro and impaired tumor growth in mice. Molecular investigations indicated that MIR210HG directly targets HIF-1α protein and inhibits VHL-dependent HIF-1α protein degradation in ovarian cancer. Further results demonstrated that MIR210HG was upregulated in ovarian cancer tissues and correlated with tumor progression and poor prognosis of ovarian cancer patients. Our study suggests that hypoxia-induced MIR210HG promotes cancer progression by inhibiting HIF-1α degradation in ovarian cancer, which could be a therapeutic target for ovarian cancer.

Mitochondrial fission causes cisplatin resistance under hypoxic conditions via ROS in ovarian cancer cells

Oncogene ◽  
2019 ◽  
Vol 38 (45) ◽  
pp. 7089-7105 ◽  
Author(s):  
Youngjin Han ◽  
Boyun Kim ◽  
Untack Cho ◽  
In Sil Park ◽  
Se Ik Kim ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Mitochondrial Fission ◽  
Ovarian Cancer Cells ◽  
Hypoxic Conditions

scholarly journals HIF2α-Sp1 interaction mediates a deacetylation-dependent FVII- gene activation under hypoxic conditions in ovarian cancer cells

2012 ◽  
Vol 40 (12) ◽  
pp. 5389-5401 ◽  
Author(s):  
Shiro Koizume ◽  
Shin Ito ◽  
Etsuko Miyagi ◽  
Fumiki Hirahara ◽  
Yoshiyasu Nakamura ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Gene Activation ◽  
Ovarian Cancer Cells ◽  
Hypoxic Conditions

Cytotoxic effects of disulfiram and synergism with cisplatin on ovarian cancer cells in vitro

2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cytotoxic Effects
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