Human pancreatic phospholipase A₂ stimulates the growth of human pancreatic cancer cell line

Abstract

Phospholipase A2 (PLA2) from human pancreas, designated hPLAz-I, functions as a digestive enzyme. Interestingly, the present study demonstrated that the mature form of hPLA2-I stimulated the growth of a human pancreatic cancer cell line MIAPaCa-2, whereas the pro-form was ineffective. PLA2s from Laticauda semifasciata fraction I, Crotalus adamanteus venom, Streptomyces violaceoruber and bee venom, showed no proliferative effect to the growth of MIAPaCa-2. The Scatchard plot analysis revealed that the MIAPaCa-2 cell had a specific binding site for the mature hPLA2-I. The equilibrium binding constant (Kd) and the maximum binding capacity (Bmax) were 2.6 nM and 0.4 fmol/10 6 cells, respectively. These results suggest that the mature hPLA2-I, but not the pro-form, may function as a growth factor of pancreas carcinoma via the specific binding site.

The N-terminal α-Helix of Pancreatic Phospholipase A2 Determines Productive-mode Orientation of the Enzyme at the Membrane Surface

“…Group IB enzymes were first found in mammalian pancreatic exudate, and therefore are known as pancreatic PLA 2 s. Although their primary function is believed to be digestion of dietary lipids, increased levels of group IB PLA 2 s have been correlated to pancreatitis and pancreatic cancer. [11][12][13][14] Secretory PLA 2 s undergo a substantial increase in activity upon binding to the surface of phospholipid micelles or membranes, an effect known as interfacial activation. [15][16][17][18] The first wten residues of PLA 2 s of certain groups, including group IB of pancreatic enzymes, form a functionally important amphipathic a-helix.…”

Secretory Phospholipase A2 Receptor-Mediated Activation of Cytosolic Phospholipase A2 in Murine Bone Marrow-Derived Mast Cells

“…Although sPLA 2 s have been studied extensively in mammals and in snake venoms, the physiological and pathophysiological roles of these enzymes are still not well known. Inspection of the numerous papers published in the past decade reveal that these sPLA 2 s have the potential to mediate a wide range of biological activities including 1) potent antibacterial effects (10,11); 2) a key component in phospholipid digestion; 3) production of lysophospholipids that contribute to electrophysiologic alterations that lead to arrhythmogenesis in the heart or altered airway permeability and surfactant properties in the lung (12-15); 4) serum markers and potential regulators of severe illnesses such as sepsis, shock, organ injury, and pancreatitis, all of which are linked to the development of adult respiratory distress syndrome and multiple organ failure (16 -19); 5) regulators of platelet aggregation in hemorrhagic diseases (20); 6) proinflammatory components in diseases such as rheumatoid arthritis and asthma (21-24); 7) markers of cancer, initiators of cell proliferation in cancer cell lines, and a potent modifying locus in intestinal tumorigenesis in mice (25)(26)(27)(28)(29)(30); and 8) enzymatic producers of arachidonic acid (AA) that contribute to eicosanoid generation (31)(32)(33)(34)(35)(36). This daunting list of activities and diseases raises fundamental questions as to whether sPLA 2 s cause or are merely associated with many of the aforementioned effects.…”

Activation of Peroxisome Proliferator-Activated Receptor Gamma Inhibits the Growth of Human Pancreatic Cancer

“…The monolayer cell proliferation assay was performed by the method described previously [22]. Briefly, 5 !…”