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.