Lack of significant differences in the corrected activity of lysophospholipase D, producer of phospholipid mediator lysophosphatidic acid, in incubated serum from women with and without ovarian tumors

Abstract

BACKGROUND Several studies have shown that lysophosphatidic acid (LPA), a phospholipidic chemical mediator, is relevant to the pathogenesis of ovarian carcinoma. Higher plasma levels of LPA have been reported in patients with ovarian carcinoma than in healthy patients, and LPA is known to activate ovarian carcinoma cells. To determine the reason for the increased plasma LPA levels in ovarian carcinoma patients, we compared the activities of serum lysophospholipase D, a novel LPA‐producing metallo‐enzyme, in healthy volunteers, patients with benign ovarian tumor, and patients with ovarian carcinoma. METHODS Lysophospholipase D activity was assessed by measuring the percentage conversion of [14C]palmitoyl‐lysophosphatidylcholine (LPC) added to human serum. The apparent enzyme activities were corrected based on the serum levels of palmitoyl‐LPC determined by gas‐liquid chromatography after its purification and conversion to fatty acid methyl esters. RESULTS The apparent activity of lysophospholipase D in serum preparations from four patients with ovarian carcinoma at Stage IV was significantly higher than those from five healthy subjects, five patients with benign ovarian tumors, and fourteen patients with ovarian carcinoma at Stages I (n = 5), II (n = 4), and III (n = 5). The serum levels of LPC, an endogenous substrate of lysophospholipase D, in ovarian carcinoma patients were less than those in patients with benign ovarian tumors. There were no significant differences in the corrected lysophospholipase D activity for the LPC levels in healthy women, patients with benign ovarian tumors, and patients with ovarian carcinoma at various stages. CONCLUSIONS The current results suggest that lysophospholipase D is not associated with the elevated plasma levels of LPA in ovarian carcinoma patients previously reported, although only a limited number of patients were analyzed. Cancer 2002;94:141–51. © 2002 American Cancer Society.

Comparative Gene Expression Analysis of Ovarian Carcinoma and Normal Ovarian Epithelium by Serial Analysis of Gene Expression

“…High levels of lysophosphatidic acid, a product of lysophospholipase catalytic activity, have been reported as a potential biomarker of ovarian cancer (33). However, lysophospholipase activity levels in serum do not seem to be associated with ovarian carcinoma (34). To our knowledge, GNAI2, GPX1, and CCT3 are not known to be overexpressed in ovarian cancer and may be entirely novel markers for this disease.…”

Metabolic pathways and physiological and pathological significances of lysolipid phosphate mediators

“…In fact, a recent report showing that the activity of serum lysoPLD in patients with ovarian cancer was almost the same as those in healthy subjects and patients with a benign ovarian tumor (Table I) [Tokumura et al, 2002b]. Previous results showing a similar elevated serum level of LPA in patients with multiple myeloma [Sasagawa et al, 1999] may indicate that increase in the LPA level in the blood circulation is not a good selective marker of ovarian cancer.…”

Submucosal connective tissue-type mast cells contribute to the production of lysophosphatidic acid (LPA) in the gastrointestinal tract through the secretion of autotaxin (ATX)/lysophospholipase D (lysoPLD)

“…extracellular conversion from other lysophospholipids. In the latter pathway, ATX/lysoPLD is shown to be a key enzyme in the production of LPA by the catalysis of LPC, which is known to be abundantly present in plasma and tissue fluids [3,64,66]. In this study, we found a subtype of MC in the human gastrointestinal tract that showed strong staining for ATX/lysoPLD.…”