Expression of group-II phospholipase A2 in malignant and non-malignant human gastric mucosa

Abstract

Summary The expression of Group-TI phospholipase A2 (M-PLA2) was analysed immunohistochemically in malignant, non-malignant (including atrophic, hyperplastic, pseudopyloric metaplastic and intestinal metaplastic) and normal human gastric mucosae. M-PLA2 was consistently detected in the stem cell lineage, pseudopyloric metaplasia and the generative cells of hyperplastic foveolar epithelium and intestinal metaplasia (IM). In IM, the appearance of Phospholipase A2 (PLA2) catalyses the specific hydrolysis of a fatty acyl ester bond at the sn-2 position of glycerophospholipids. In addition, a calcium-dependent PLA2 is thought to be one of the most important enzymes regulating the release of arachidonic acid from membrane phospholipids (Lands, 1968; Van den Bosh, 1980). Until recently, two genetically distinct isoenzymes, exocrine PLA2 (secreted in pancreatic juice) and intracellular PLA2 (contained in the cytosol and membrane-associated fraction), have been recognised in humans (Vadas & Pruzanski, 1986;Nakaguchi et al., 1986). In the membrane fraction of human spleen cells the existence of a PLA2, which does not react with anti-human P-PLA2 antibody, has been demonstrated (Nakaguchi et al., 1986). Further purification and subsequent sequencing of this enzyme revealed that it belongs to the Group-I1 PLA2 (Kanda et al., 1989). Group-II PLA2 has been thought to play an important regulatory role in several metabolic pathways (Nakano et al., 1990a;Nakano et al., 1990b). And recently, the distribution of this Group-II-PLA2 in human organs has been published (Kiyohara et al., 1992).The product of this enzyme's action, free arachidonate (which serves as a substrate for the cyclo-oxygenase route and lipoxygenase route) (Van den Bosh, 1980) is the first and rate-limiting precursor in the biosynthes of prostaglandins (PG), leukotriene and HETE (Lands, 1979; Van den Bosh, 1980). Among these products, PG is abundant in gastrointestinal mucosa (Robert et al., 1979), and especially PGE2, has potent cytoprotective effects, e.g. inhibition of gastric secretion, prevention of ulcer formation, and acceleration of the healing of mucosal damage (Robert et al., 1979;Wilson et al., 1971;Robert et al., 1976). Nevertheless, the biological significance and function of PLA2 in the human stomach is still unknown. In the rat gastric mucosa, PLA2 which is structurally identical to the rat pancreatic type PLA2 (P-PLA2, Group-I PLA2) (Tojo et al., 1988;Okamoto et al., 1985) was immunocytochemically detected in chief cells (Tatsumi et al., 1990). Knowledge of the distribution of this enzyme in human gastric mucosa might provide useful insight into the function of PLA2 in gastric mucosa.In this study, the immunohistochemical expression of M-PLA2 was examined by using a monoclonal antibody (MoAb) against the recently described human splenic Group-II PLA2 (M-PLA2) in a variety of human gastric mucosae, such as normal, atrophic, hyperplastic, pseudopyloric metaplastic and intestinal metaplastic mucosae, as well as cancerous lesions. Moreover, the po...

Expression of inflammatory secretory phospholipase A2 and cytosolic phospholipase A2 in premalignant and malignant Barrett?s oesophagus

“…These results are in accordance with previous data showing an absence or a very weak sPLA2 and cPLA2 expression in the epithelial cells of the normal colonic mucosa [41]. sPLA2 was strongly expressed in Paneth cells, as it has been previously reported [21,29]. The increasing rate of sPLA2 and to a lesser extent of cPLA2 that we observed during morphological steps of Barrett's carcinogenesis is in agreement with preliminary data demonstrating that COX-2 expression is enhanced in Barrett's mucosa and increases as the neoplastic process progresses to intraepithelial neoplasia and to adenocarcinoma [27,33].…”

“…Overexpression of sPLA2 has been reported in several types of digestive cancers. There is increased sPLA2 expression in gastric adenocarcinoma, small-bowel adenocarcinoma, hepatocellular carcinoma and pancreatic adenocarcinoma [18,25,29,41,44]. The upregulation of sPLA2 in our study is also consistent with the frequent enhanced expression of COX-2 reported in Barrett's adenocarcinoma [23,27,33].…”

Both Group IB and Group IIA Secreted Phospholipases A2 Are Natural Ligands of the Mouse 180-kDa M-type Receptor

“…Group IIA sPLA 2 is also referred to as the inflammatory-type sPLA 2 , since it is highly expressed in the plasma and synovial fluids of patients with various inflammatory diseases such as rheumatoid arthritis, acute pancreatitis, Crohn's disease, and endotoxic shock (3, 14 -16) as well as in various cancers (17,18). The group IIA sPLA 2 has been shown to participate in the production of lipid mediators of inflammation (3,19,20) and in the destruction of pathogenic microorganisms (21).…”

Enhancement of paclitaxel activity against hormone-refractory prostate cancer cells in vitro and in vivo by quinacrine

“…PLA2 hydrolyses the sn-2-acyl bond of membrane phospholipids to produce arachidonic acid, which has been implicated in a variety of signal transduction events, including malignant cell proliferation (Tokumoto et al, 1993;Hanada et al, 1995). Further, histological studies suggest that membrane PLA2 expression is associated with the aggressiveness of tumour type, at least in gastric (Yamashita et al, 1994) and breast cancer (Murata et al, 1993). The regulation of cytoplasmic PLA2 (cPLA2) is complex, but the enzyme is known to be phosphorylated and activated by MAP kinase (Lin et al, 1993), which is itself a downstream component of ras cellular signalling.…”