Role of the Phospholipase A₂ Receptor in Liposome Drug Delivery in Prostate Cancer Cells

Abstract

The M-type phospholipase A2 receptor (PLA2R1) is a member of the C-type lectin superfamily and can internalize secreted phospholipase A2 (sPLA2) via endocytosis in non-cancer cells. sPLA2 itself was recently shown to be overexpressed in prostate tumors and to be a possible mediator of metastasis; however, little is known about the expression of PLA2R1 or its function in prostate cancers. Thus, we examined PLA2R1 expression in primary prostate cells (PCS-440-010) and human prostate cancer cells (LNCaP, DU-145, and PC-3), and we determined the effect of PLA2R1 knockdown on cytotoxicity induced by free or liposome-encapsulated chemotherapeutics. Immunoblot analysis demonstrated that the expression of PLA2R1 was higher in prostate cancer cells compared to that in primary prostate cells. Knockdown of PLA2R1 expression in PC-3 cells using shRNA increased cell proliferation and did not affect the toxicity of cisplatin, doxorubicin (Dox), and docetaxel. In contrast, PLA2R1 knockdown increased the in vitro toxicity of Dox encapsulated in sPLA2 responsive liposomes (SPRL) and correlated with increased Dox and SPRL uptake. Knockdown of PLA2R1 also increased the expression of Group IIA and X sPLA2. These data show the novel findings that PLA2R1 is expressed in prostate cancer cells, that PLA2R1 expression alters cell proliferation, and that PLA2R1 modulates the behavior of liposome-based nanoparticles. Furthermore, these studies suggest that PLA2R1 may represent a novel molecular target for controlling tumor growth or modulating delivery of lipid-based nanomedicines.

Liposome-mediated delivery of the p21 activated kinase-1 (PAK-1) inhibitor IPA-3 limits prostate tumor growth in vivo

“…Analysis of zeta potential and size indicated that these nanoparticles would be functional for clinical application, and the activity of these formulations were verified in vitro . It is not surprising that SSL-IPA-3 were not as effective as free IPA-3 in vitro and in vivo , as this is commonly seen in many studies, including those reported from our own laboratory 16, 22, 29 . What was surprising was that the effect of SSL-IPA-3 was shown to be cell type-dependent and mediated by the level of expression of PAK-1.…”

Epigenetic control of phospholipase A2 receptor expression in mammary cancer cells

“…PLA2R1 expression was found decreased in leukaemia, mammary, renal and thyroid cancers [ 9 , 12 – 15 ]. While the receptor is down-regulated in these cancers, significant up-regulation of PLA2R1 was described in the prostate cancer cell lines PC-3 and DU-145 in comparison to normal prostate cells [ 16 ]. High expression of PLA2R1 was also identified in ovarian carcinoma effusions, human leukemic blasts and dermatofibrosarcoma [ 17 – 19 ].…”

A Nano-Platform for in situ Investigations of Ovarian Follicles

“…Fluorescence liposome formulation. Pegylated liposomes were prepared as previously described 249 [41,42]. Briefly, formulations were generated according to a ratio of 10 µmol DPPC, injected into each growing follicle using a double-channel injection system as previously described [4,44].…”