Lysophosphatidic acid enhances epithelial ovarian carcinoma invasion through the increased expression of interleukin-8

So, John; Navari, Jason R.; Wang, Feng-Qiang; Fishman, David A.

doi:10.1016/j.ygyno.2004.08.001

Cited by 65 publications

(41 citation statements)

References 22 publications

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“…The above CM samples, were evaluated for functional activity of MMPs by gelatin zymography as previously described [8]. CM samples (32µl) were electrophoresed at 26mA on 9% SDS--polyacrylamide gels containing 0.1% porcine skin gelatin (Sigma, St Louis, MO).…”

Section: Gel Zymographymentioning

confidence: 99%

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S1P induced changes in epithelial ovarian cancer proteolysis, invasion, and attachment are mediated by Gi and Rac

Devine

Smicun

Hope

et al. 2008

Gynecologic Oncology

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OBJECTIVES-We previously demonstrated that sphingosine 1-phosphate (S1P) bimodally regulates epithelial ovarian cancer (EOC) cell invasiveness: low-concentration S1P stimulates invasion similar to lysophophatidic acid (LPA), while high-concentration S1P inhibits invasion. In this study, we investigated the mechanisms through which S1P affects EOC cell proteolysis, invasion, and adhesion in two cultured epithelial ovarian cancer cell lines. METHODS-G-proteinGi was inhibited by pertussis toxin (PTX) and GTP binding protein Rac by NSC23766. S1P conditioned media of DOV13 and OVCA429 cells were evaluated via gel zymography, fluorometric gelatinase assay, urokinase plasminogen activator (uPA) activity assay, and Western Blot for MT1-MMP. Cell invasion was analyzed in Matrigel chambers. Membrane-N-cadherin was localized via fluorescence microscopy.RESULTS-Zymography revealed pro-MMP2 in conditioned media of EOC cells regardless of treatment. Gelatinase activity was increased by low-concentration S1P. In DOV13 cells this effect was Gi and Rac dependent. In all OVCA429 and control DOV13 cells, PTX enhanced gelatinolysis, suggesting an MMP2-inhibitory pathway via Gi. MT1-MMP was decreased Gidependently by high-concentration S1P. Rac inhibition significantly counteracted low-S1P enhancement and high-S1P reduction of DOV13 invasiveness; and uPA activity in conditioned media of invading cells correlated significantly. Immunohistochemistry revealed Gi-dependent clustering of membrane-N-cadherin in DOV13 cells treated with 0.5µM S1P or 10µM LPA.CONCLUSIONS-S1P influences EOC invasion by regulating ECM-proteolysis and cell-cell attachment via MMP2, uPA, and membrane-N-cadherin. Furthermore, this study illustrates that the net effect of S1P on each of these processes reflects a complex interplay of multiple GPCR pathways involving Gi and downstream Rac.

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Section: Gel Zymographymentioning

confidence: 99%

“…Both LPA and S1P are found in high levels in malignant ovarian ascites, have similar enhancing effects on proliferation, and repression of apoptosis in vitro, and affect invasion [4][5][6][7][8][9]. LPA and S1P have potential beyond their mechanistic role in EOC progression as diagnostic and prognostic biomarkers [4,10,11].…”

Section: Introductionmentioning

confidence: 99%

S1P induced changes in epithelial ovarian cancer proteolysis, invasion, and attachment are mediated by Gi and Rac

Devine

Smicun

Hope

et al. 2008

Gynecologic Oncology

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“…We and others have shown that LPA stimulates the migration and invasion of ovarian cancer cells (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Although most, if not all, of these studies were conducted in established ovarian cancer cell lines, we have recently conducted LPA-and S1P-induced cell migration and invasion experiments in primary EOC and nonmalignant human ovarian surface epithelial cells (11,23).…”

Section: Introductionmentioning

confidence: 99%

Lysophosphatidic acid stimulates cell migration, invasion, and colony formation as well as tumorigenesis/metastasis of mouse ovarian cancer in immunocompetent mice

Wang

Zhang

et al. 2009

Molecular Cancer Therapeutics

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We have already established human xenographic models for the effect of lysophosphatidic acid (LPA) on tumor metastasis in vivo. The purpose of this work is to establish a preclinical LPA effect model in immunocompetent mice. We first characterized the mouse epithelial ovarian cancer (EOC) cell line ID8 for its responsiveness to LPA in cell proliferation, migration, and invasion and compared these properties with those of human EOC. The signaling pathways related to cell migration were further investigated using pharmacologic and genetic approaches. The effects of LPA on the tumorigenesis of ID8 cells and mouse survival were then examined using two different mouse models (i.p. and orthotopic injections). LPA stimulated cell proliferation, migration, and invasion of mouse EOC ID8 cells in a manner closely resembling its activity in human EOC cells. The signaling pathways involved in LPAinduced cell migration in ID8 cells were also similar to those identified in human EOC cells. We have identified cyclooxygenase-1 and 15-lipoxygenase as two new signaling molecules involved in LPA-induced cell migration in both human and mouse EOC cells. In addition, LPA enhanced the tumorigenesis/metastasis of ID8 cell in vivo as assessed by increased tumor size, early onset of ascites formation, and reduced animal survival. We have established the first LPA-EOC preclinical model in immunocompetent mice. Because ID8 cells respond to LPA similar to human EOC cells, this model is very valuable in developing and testing therapeutic reagents targeting LPA in

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“…Other reports also found that LPA could induce the expression of vascular endothelial growth factor and IL-8 (43,45). Thus, we hypothesized that MMP-7 secretion and activation may be regulated by LPA.…”

Section: Introductionmentioning

confidence: 75%

“…We previously reported that the proangiogenic molecules vascular endothelial growth factor and interleukin (IL)-8 induce the secretion/activation of MMP-7 in EOC (43,44). Other reports also found that LPA could induce the expression of vascular endothelial growth factor and IL-8 (43,45).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Matrilysin Expression by Antisense or RNA Interference Decreases Lysophosphatidic Acid–Induced Epithelial Ovarian Cancer Invasion

Wang

Smicun

Calluzzo

et al. 2006

Molecular Cancer Research

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Our previous reports show that matrilysin [matrix metalloproteinase (MMP)-7] is overexpressed in epithelial ovarian cancer (EOC) and recombinant MMP-7 promotes EOC invasion in vitro. In the present study, we further evaluated the correlation of MMP-7 expression to EOC invasiveness and examined its role in lysophosphatidic acid (LPA)-induced invasion. By sense and antisense gene transfection in vitro, we show that overexpression of MMP-7 in all MMP-7 stably transfected DOV13 clones significantly enhanced their invasiveness, although MMP-7 antisense transfection caused a 91% decrease of MMP-7 expression (P < 0.01) and 87% decrease of invasion (P < 0.05) in geneticin (G418)-selected DOV13 clone P47-M7As-3 compared with vector-transfected control.As assessed by MMP-7 ELISA, LPA treatment at 10 to 80 Mmol/L significantly stimulated the secretion of total MMP-7 in DOV13 conditioned medium (P < 0.01). In addition, LPA apparently induced the activation of MMP-7 in DOV13 cells as detected by gelatin zymography. In the antisense MMP-7-transfected DOV13 clone (P47-M7As-3), LPA-increased invasion was significantly decreased compared with vector control. Moreover, knocking down of MMP-7 by small interfering RNA also suppressed LPA-induced invasion in two EOC cell lines (DOV13 and R182). Altogether, our results show that MMP-7 expression is correlated with EOC invasiveness and LPA-induced MMP-7 secretion/ activation may represent a new mechanism that facilitates ovarian cancer invasion besides the well-known induction of MT1-MMP-mediated proMMP-2 activation by LPA. (Mol Cancer Res 2006;4(11):831 -41)

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Lysophosphatidic acid enhances epithelial ovarian carcinoma invasion through the increased expression of interleukin-8

Cited by 65 publications

References 22 publications

S1P induced changes in epithelial ovarian cancer proteolysis, invasion, and attachment are mediated by Gi and Rac

S1P induced changes in epithelial ovarian cancer proteolysis, invasion, and attachment are mediated by Gi and Rac

Lysophosphatidic acid stimulates cell migration, invasion, and colony formation as well as tumorigenesis/metastasis of mouse ovarian cancer in immunocompetent mice

Inhibition of Matrilysin Expression by Antisense or RNA Interference Decreases Lysophosphatidic Acid–Induced Epithelial Ovarian Cancer Invasion

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