Lysophosphatidic Acid Disrupts Junctional Integrity and Epithelial Cohesion in Ovarian Cancer Cells

Ovarian cancer metastasizes via exfoliation of free-floating cells and multicellular aggregates from the primary tumor to the peritoneal cavity. A key event in EOC metastasis is disruption of cell-cell contacts via modulation of intercellular junctional components including cadherins. Ascites is rich in lysophosphatidic acid (LPA), a bioactive lipid that may promote early events in ovarian cancer dissemination. The objective of this paper was to assess the effect of LPA on E-cadherin junctional integrity. We report a loss of junctional E-cadherin in OVCAR3, OVCA429, and OVCA433 cells exposed to LPA. LPA-induced loss of E-cadherin was concentration and time dependent. LPA increased MMP-9 expression and promoted MMP-9-catalyzed E-cadherin ectodomain shedding. Blocking LPA receptor signaling inhibited MMP-9 expression and restored junctional E-cadherin staining. LPA-treated cells demonstrated a significant decrease in epithelial cohesion. Together these data support a model wherein LPA induces MMP-9 expression and MMP-9-catalyzed E-cadherin ectodomain shedding, resulting in loss of E-cadherin junctional integrity and epithelial cohesion, facilitating metastatic dissemination of ovarian cancer cells.

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Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells

Neoplasia ◽

10.1016/j.neo.2015.09.003 ◽

2015 ◽

Vol 17 (9) ◽

pp. 723-734 ◽

Cited By ~ 25

Author(s):

Abir Mukherjee ◽

Yibao Ma ◽

Fang Yuan ◽

Yongling Gong ◽

Zhenyu Fang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Lysophosphatidic Acid ◽

Ovarian Cancer Cells ◽

Hexokinase Ii

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E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway

Acta Pharmacologica Sinica ◽

10.1038/aps.2012.30 ◽

2012 ◽

Vol 33 (6) ◽

pp. 817-822 ◽

Cited By ~ 22

Author(s):

Ling-ling Dong ◽

Lian Liu ◽

Chun-hong Ma ◽

Ji-sheng Li ◽

Chao Du ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Erk Pathway ◽

E Cadherin

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In vitro effect of lysophosphatidic acid on proliferation, invasion and migration of human ovarian cancer cells

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v17i2.4 ◽

2018 ◽

Vol 17 (2) ◽

pp. 219

Author(s):

Qingfu Wang ◽

Lixin Zhu ◽

Aiping Qin ◽

Tiefeng Chen ◽

Jinpen Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Lysophosphatidic Acid ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Invasion And Migration ◽

And Migration

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Lysophosphatidic acid activates telomerase in ovarian cancer cells through hypoxia-inducible factor-1α and the PI3K pathway

Journal of Cellular Biochemistry ◽

10.1002/jcb.21919 ◽

2008 ◽

Vol 105 (5) ◽

pp. 1194-1201 ◽

Cited By ~ 21

Author(s):

Kun Yang ◽

Danhua Zheng ◽

Xiaoli Deng ◽

Lin Bai ◽

Yan Xu ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Lysophosphatidic Acid ◽

Hypoxia Inducible Factor ◽

Pi3k Pathway ◽

Ovarian Cancer Cells ◽

Hypoxia Inducible Factor 1Α

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215 SNAIL AND SLUG, MARKERS OF EPITHELIAL MESENCHYMAL TRANSITION, APPEARED TO BE ALTERED BY ALKYL-PHENOLS, BISPHENOL A AND NONYL-PHENOL, IN OVARIAN CANCER CELLS EXPRESSING ESTROGEN RECEPTORS

Reproduction Fertility and Development ◽

10.1071/rdv27n1ab215 ◽

2015 ◽

Vol 27 (1) ◽

pp. 198 ◽

Cited By ~ 1

Author(s):

Y.-S. Kim ◽

K.-C. Choi

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Ovarian Cancer Cells ◽

Rt Pcr ◽

Nonyl Phenol ◽

Mesenchymal Transition ◽

And Migration ◽

Emt Markers ◽

E Cadherin

The ovary is the important organ to produce oocytes. Any disorder will affect embryo production. Ovarian cancer is one of gynecologic cancers in women which can affect ovarian functions. Oestradiol (E2) may be involved in ovarian cell growth and epithelial-mesenchymal transition (EMT) for diverse functions. EMT is an important process in embryo development and tumour migration or progression. Bis-phenol A (BPA) and nonyl-phenol (NP) have an estrogenic property, which can be suspected as endocrine disrupting chemicals (EDC). In this study, it has been examined whether BPA and NP can cause EMT process and migration in BG-1 ovarian cancer cells. To confirm the effect of these EDCs, BG-1 ovarian cancer cells were cultured and treated with DMSO (0.1%), E2 (10–7 M), BPA (10–6 M) and NP (10–6 M) for 0, 6, and 24 h. The mRNAs were extracted to perform reverse-transcription (RT)-PCR and the changes in the mRNA expressions were analysed by ANOVA test. Following treatments with BPA and NP, alterations of EMT markers; that is, vimentin and E-cadherin, were examined at mRNA levels by RT-PCR. The levels of vimentin were up-regulated by E2, BPA, or NP in a time-dependent manner. In addition, transcriptional factors of EMT response, i.e. snail and slug, were enhanced by these treatments more than 2 times. BG-1 cells were exposed to these EDCs for 0, 24, and 48 h. Vimentin and snail proteins were induced by E2, BPA, or NP, while the expression of E-cadherin was decreased by them. To reveal that this EMT response is affected by oestrogen receptor (ER), the cells were treated with these EDCs in the presence of an ER antagonist, ICI 182 780 (10–6 M). Treatment with ICI 182 780 reversed EDC-induced alteration of these EMT markers, E-cadherin, vimentin, and snail. Since EMT response can cause metastasis, a scratch assay was performed to show migration caused by BPA or NP. BPA or E2 enhanced migratory capability of these BG-1 cells. Taken together, these results indicate that BPA and NP, potential EDC, may have an ability to influence ovarian cancer metastasis via regulating snail and slug genes in ER-positive ovarian cancers. In a future study, their effects in inducing EMT and migration will be tested in a xenograft mouse model.This work was supported by a grant from the Next-Generation BioGreen 21 Program (no. PJ009599), Rural Development Administration, Republic of Korea.

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