TY - JOUR
T1 - Lysophospholipids increase interleukin-8 expression in ovarian cancer cells
AU - Schwartz, Benjamin M.
AU - Hong, Guiying
AU - Morrison, Bei H.
AU - Wu, Weihua
AU - Baudhuin, Linnea M.
AU - Xiao, Yi Jin
AU - Mok, Samuel C.
AU - Xu, Yan
N1 - Funding Information:
1Supported in part by American Cancer Society Grant RPG-99-062-01-CNE, U.S. Army Grant DAMD17-99-1-9653, and a grant from the Malcolm Hewitt Wiener Foundation, New York, to Y.X., and by Betsy De Windt Endowment Funds to the Department of Cancer Biology, Cleveland Clinic Foundation. 2Current address: Taussig Cancer Center, Cleveland Clinic Foundation.
PY - 2001
Y1 - 2001
N2 - Objectives. We have previously described that bioactive lysophospholipids - lysophosphatidic acid (LPA), sphingosine 1-phosphate (SIP), and sphingosylphosphorylcholine (SPC) - are present in ascitic fluids from patients with ovarian cancer. To understand the role of these lipids in ovarian cancer, we investigated the effects of these lipids on interleukin-8 (IL-8) production in ovarian cancer cells. IL-8 is a proinflammatory and proangiogenic factor, which is potentially involved in ovarian cancer development. Methods. The Clontech PCR-Select cDNA subtraction method (Clontech Laboratories, Inc., Palo Alto, CA) was used to identify genes potentially regulated by LPA in HEY and OCC1 ovarian cancer cell lines. Northern blot analysis was used to confirm and examine IL-8 mRNA regulation by lysolipids. Enzyme-linked immunosorbent assay (ELISA) was used for detecting secreted IL-8. Results. We describe here that LPA, S1P, and SPC increased mRNA levels (2- to 7-fold) and protein secretion (2- to 12-fold) of IL-8 from ovarian cancer cells (HEY, OCC1, and SKOV3) in vitro. These regulations were both dose- and time-dependent. All three lipids increased the stability IL-8 mRNA in HEY cells. In contrast to malignant ovarian cancer cells, immortalized human ovarian epithelial cells did not respond to any of these lipids to increase the secretion of IL-8, although these cells secreted similar basal levels of IL-8 (310 pg/ml/10,000 cells). Two breast cancer cell lines (MCF7 and T47D) secreted lower basal levels of IL-8 (48-80 pg/ml/10,000 cells), compared with ovarian cancer cells (200-500 pg/ml/10,000 cells). MCF7 cells responded to LPA, but not S1P and SPC, by increasing the secretion of IL-8. T47D and MCF10A, an immortalized breast cell line, did not respond to LPA, S1P, or SPC to increase IL-8 secretion. Conclusions. LPA, S1P, and SPC regulate the mRNA and protein levels of the proinflammatory and proangiogenic factor IL-8 in ovarian cancer cells. The pathological significance of these regulations in ovarian cancer remains to be further investigated.
AB - Objectives. We have previously described that bioactive lysophospholipids - lysophosphatidic acid (LPA), sphingosine 1-phosphate (SIP), and sphingosylphosphorylcholine (SPC) - are present in ascitic fluids from patients with ovarian cancer. To understand the role of these lipids in ovarian cancer, we investigated the effects of these lipids on interleukin-8 (IL-8) production in ovarian cancer cells. IL-8 is a proinflammatory and proangiogenic factor, which is potentially involved in ovarian cancer development. Methods. The Clontech PCR-Select cDNA subtraction method (Clontech Laboratories, Inc., Palo Alto, CA) was used to identify genes potentially regulated by LPA in HEY and OCC1 ovarian cancer cell lines. Northern blot analysis was used to confirm and examine IL-8 mRNA regulation by lysolipids. Enzyme-linked immunosorbent assay (ELISA) was used for detecting secreted IL-8. Results. We describe here that LPA, S1P, and SPC increased mRNA levels (2- to 7-fold) and protein secretion (2- to 12-fold) of IL-8 from ovarian cancer cells (HEY, OCC1, and SKOV3) in vitro. These regulations were both dose- and time-dependent. All three lipids increased the stability IL-8 mRNA in HEY cells. In contrast to malignant ovarian cancer cells, immortalized human ovarian epithelial cells did not respond to any of these lipids to increase the secretion of IL-8, although these cells secreted similar basal levels of IL-8 (310 pg/ml/10,000 cells). Two breast cancer cell lines (MCF7 and T47D) secreted lower basal levels of IL-8 (48-80 pg/ml/10,000 cells), compared with ovarian cancer cells (200-500 pg/ml/10,000 cells). MCF7 cells responded to LPA, but not S1P and SPC, by increasing the secretion of IL-8. T47D and MCF10A, an immortalized breast cell line, did not respond to LPA, S1P, or SPC to increase IL-8 secretion. Conclusions. LPA, S1P, and SPC regulate the mRNA and protein levels of the proinflammatory and proangiogenic factor IL-8 in ovarian cancer cells. The pathological significance of these regulations in ovarian cancer remains to be further investigated.
KW - Interleukin-8
KW - Lysophosphatidic acid
KW - Ovarian cancer
KW - Sphingosine 1-phosphate
KW - Sphingosylphosphorylcholine (SPC)
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U2 - 10.1006/gyno.2001.6124
DO - 10.1006/gyno.2001.6124
M3 - Article
C2 - 11330965
AN - SCOPUS:0035025317
SN - 0090-8258
VL - 81
SP - 291
EP - 300
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 2
ER -