Abstract
Several studies indicate that phospholipase A2 (PLA2) expression and/or activation account for the high levels of arachidonic acid (AA) detected in cancer and, together with the elevated expression of cyclooxygenase-2, lead to cell proliferation and tumor formation. Using Caco-2 cells, a human colorectal carcinoma cell, we studied the role of high-molecular-weight PLA2s, cytosolic PLA2 (cPLA2), and calcium-independent PLA2 (iPLA2) in the AA cascade and in cell growth. Treatment with an antisense oligonucleotide against cPLA2α decreased [3H]AA release induced by ionophore A23187 or by a phorbol ester but did not affect the release of [3H]AA, [3H]thymidine incorporation, or Caco-2 growth induced by fetal calf serum (FCS). However, these parameters were significantly modified by iPLA2 inhibitors and by an antisense oligonucleotide against iPLA2β. Our results show that iPLA2 was involved in AA release and the subsequent prostaglandin production induced by serum. Moreover, these data indicate that iPLA2 may be involved in the signaling pathways involved in the control of Caco-2 proliferation.