Unknown

Dataset Information

0

SPARC inhibits LPA-mediated mesothelial-ovarian cancer cell crosstalk.


ABSTRACT: The interplay between peritoneal mesothelial cells and ovarian cancer cells is critical for the initiation and peritoneal dissemination of, and ascites formation in, ovarian cancer. The production of lysophosphatidic acid (LPA) by both peritoneal mesothelial cells and ovarian cancer cells has been shown to promote metastatic phenotype in ovarian cancer. Herein, we report that exogenous addition or ectopic overexpression of the matricellular protein SPARC (secreted protein acidic and rich in cysteine) significantly attenuated LPA-induced proliferation, chemotaxis, and invasion in both highly metastatic SKOV3 and less metastatic OVCAR3 ovarian cancer cell lines. SPARC appears to modulate these functions, at least in part, through the regulation of LPA receptor levels and the attenuation of extracellular signal-regulated kinase (ERK) 1/2 and protein kinase B/AKT signaling. Moreover, our results show that SPARC not only significantly inhibited both basal and LPA-induced interleukin (IL) 6 production in both cell lines but also attenuated IL-6-induced mitogenic, chemotactic, and proinvasive effects, in part, through significant suppression of ERK1/2 and, to a lesser extent, of signal transducers and activators of transcription 3 signaling pathways. Our results strongly suggest that SPARC exerts a dual inhibitory effect on LPA-induced mesothelial-ovarian cancer cell crosstalk through the regulation of both LPA-induced IL-6 production and function. Taken together, our findings underscore the use of SPARC as a potential therapeutic candidate in peritoneal ovarian carcinomatosis.

SUBMITTER: Said NA 

PROVIDER: S-EPMC1803033 | BioStudies | 2007-01-01

REPOSITORIES: biostudies

Similar Datasets

2020-01-01 | S-EPMC7331713 | BioStudies
1000-01-01 | S-EPMC1864881 | BioStudies
2010-01-01 | S-EPMC3059077 | BioStudies
2017-01-01 | S-EPMC5343481 | BioStudies
2014-01-01 | S-EPMC4038562 | BioStudies
2015-01-01 | S-EPMC4649895 | BioStudies
2016-01-01 | S-EPMC5021370 | BioStudies
2018-01-01 | S-EPMC6030435 | BioStudies
2015-01-01 | S-EPMC4698803 | BioStudies
2008-01-01 | S-EPMC2720766 | BioStudies