Expression of secretory phospholipase A2 in colon tumor cells potentiates tumor growth.
Secretory phospholipase A2 (sPLA2-IIA) has been shown to attenuate intestinal tumorigenesis in Apc(Min) mice, demonstrating that it is a tumor modifier. To further explore the actions of sPLA2-IIA in tumorigenesis, sPLA2-IIA was overexpressed in two cell lines where it is normally absent, the murine colon tumor cell line AJ02nm0, and human colon carcinoma cell line HCT-116. Two allelic variants of sPLA2-IIA were tested in this study; sPLA2-IIA(AKR) and sPLA2-IIA(SWR), which are derived from AKR/J and SWR/J mice, respectively, and differ by a single amino acid at position 63 in the calcium- and receptor-binding domain. There was no change in cell-doubling time for either allele when compared to vector controls. Furthermore, sodium butyrate and arachidonic acid (AA)-induced cell death were unchanged in control and transfected cells. Addition of the sPLA2 substrate, palmitoyl-arachidonoyl-phosphatidic acid (PAPA), to AJ02nm0 cells resulted in a modest (12%-24%), but significant (P < 0.01), inhibition of growth that was dependent on sPLA2-IIA expression. However, when AJ02nm0 and HCT-116 cells were injected subcutaneously (sc) into nude mice, Pla2g2a expression resulted in a 2.5-fold increase in tumor size. In addition, sPLA2-IIA expressing HCT-116 tumors were found to be more infiltrative than controls. We conclude that the ability of sPLA2-IIA to slow tumor cell growth is dependent upon the availability of substrate, and that in some instances sPLA2-IIA may actually enhance tumor growth. Mechanisms that may account for differences between the tumor explant model versus the Apc(Min) model of intestinal cancer are discussed.
Belinsky
Glenn S
GS
Center for Molecular Medicine, The Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, Connecticut 06030-3101, USA.
Rajan
Thiruchandurai V
TV
Saria
Elizabeth A
EA
Giardina
Charles
C
Rosenberg
Daniel W
DW
D016718:Arachidonic Acid / Q000494:pharmacology; D001483:Base Sequence; D020148:Butyric Acid / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D017931:DNA Primers; D054501:Group II Phospholipases A2; D006801:Humans; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017931:DNA Primers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020148:Butyric Acid; D016718:Arachidonic Acid; D010741:Phospholipases A; D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human; D054467:Phospholipases A2