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.
Subject(s)
Drug Delivery Systems/methods , Liposomes/administration & dosage , Prostatic Neoplasms/enzymology , Receptors, Phospholipase A2/metabolism , Blotting, Western , Cell Line, Tumor , Humans , Male , Nanoparticles/chemistry , Receptors, Phospholipase A2/genetics , Tumor Cells, CulturedABSTRACT
Melanin was measured by a spectrophotofluorometric method in the brains of albino rats from birth to 20 months of age. The concentration of brain melanin increased from Day 1 until adult levels were reached at 1 month. Between 1 and 20 months of age no significant differences were found in brain melanin. Daily injections of alpha-MSH, MIF-I, melatonin, or diluent did not consistently alter the concentration of brain melanin and a high (40%) protein diet did not appear to increase it. After concurrent injections of alpha-MSH and theophylline, an initial elevation of the level of melanin in the brain of newborn rats was found beginning at Day 8 but by age 1 month the values had returned to control levels. The results show that the largest changes in the concentrations of melanin in the brains of rats occur with age during the first month after birth.
