SPARC Inhibits LPA-Mediated Mesothelial—Ovarian Cancer Cell Crosstalk
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 s...
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| Format: | Article |
| Language: | English |
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Elsevier
2007-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558607800133 |
| _version_ | 1818113402269073408 |
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| author | Neveen A. Said Ida Najwer Matthew J. Socha David J. Fulton Samuel C. Mok Kouros Motamed |
| author_facet | Neveen A. Said Ida Najwer Matthew J. Socha David J. Fulton Samuel C. Mok Kouros Motamed |
| author_sort | Neveen A. Said |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T03:34:16Z |
| format | Article |
| id | doaj.art-f4400990d46b4fbfabd2c3303b75e5ea |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-11T03:34:16Z |
| publishDate | 2007-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-f4400990d46b4fbfabd2c3303b75e5ea2022-12-22T01:22:19ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022007-01-0191233510.1593/neo.06658SPARC Inhibits LPA-Mediated Mesothelial—Ovarian Cancer Cell CrosstalkNeveen A. Said0Ida Najwer1Matthew J. Socha2David J. Fulton3Samuel C. Mok4Kouros Motamed5Vascular Biology Center, Medical College of Georgia, Augusta, GA, USAVascular Biology Center, Medical College of Georgia, Augusta, GA, USAVascular Biology Center, Medical College of Georgia, Augusta, GA, USAVascular Biology Center, Medical College of Georgia, Augusta, GA, USABrigham and Women's Hospital, Harvard Medical School, Boston, MA, USAVascular Biology Center, Medical College of Georgia, Augusta, GA, USAThe 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.http://www.sciencedirect.com/science/article/pii/S1476558607800133SPARCLPAIL-6ovarian cancermesothelial cells |
| spellingShingle | Neveen A. Said Ida Najwer Matthew J. Socha David J. Fulton Samuel C. Mok Kouros Motamed SPARC Inhibits LPA-Mediated Mesothelial—Ovarian Cancer Cell Crosstalk Neoplasia: An International Journal for Oncology Research SPARC LPA IL-6 ovarian cancer mesothelial cells |
| title | SPARC Inhibits LPA-Mediated Mesothelial—Ovarian Cancer Cell Crosstalk |
| title_full | SPARC Inhibits LPA-Mediated Mesothelial—Ovarian Cancer Cell Crosstalk |
| title_fullStr | SPARC Inhibits LPA-Mediated Mesothelial—Ovarian Cancer Cell Crosstalk |
| title_full_unstemmed | SPARC Inhibits LPA-Mediated Mesothelial—Ovarian Cancer Cell Crosstalk |
| title_short | SPARC Inhibits LPA-Mediated Mesothelial—Ovarian Cancer Cell Crosstalk |
| title_sort | sparc inhibits lpa mediated mesothelial ovarian cancer cell crosstalk |
| topic | SPARC LPA IL-6 ovarian cancer mesothelial cells |
| url | http://www.sciencedirect.com/science/article/pii/S1476558607800133 |
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