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Prostate cancer targeting motifs: Expression of α ν β 3 , neurotensin receptor 1, prostate specific membrane antigen, and prostate stem cell antigen in human prostate cancer cell lines and xenografts
Author(s) -
Taylor Robert M.,
Severns Virginia,
Brown David C.,
Bisoffi Marco,
Sillerud Laurel O.
Publication year - 2012
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21454
Subject(s) - lncap , prostate cancer , cancer research , biology , pca3 , prostate , cancer , microbiology and biotechnology , genetics
BACKGROUND Membrane receptors are frequent targets of cancer therapeutic and imaging agents. However, promising in vitro results often do not translate to in vivo clinical applications. To better understand this obstacle, we measured the expression differences in receptor signatures among several human prostate cancer cell lines and xenografts as a function of tumorigenicity. METHODS Messenger RNA and protein expression levels for integrin α ν β 3 , neurotensin receptor 1 (NTSR1), prostate specific membrane antigen (PSMA), and prostate stem cell antigen (PSCA) were measured in LNCaP, C4‐2, and PC‐3 human prostate cancer cell lines and in murine xenografts using quantitative reverse transcriptase polymerase chain reaction, flow cytometry, and immunohistochemistry. RESULTS Stable expression patterns were observed for integrin α ν and PSMA in all cells and corresponding xenografts. Integrin β 3 mRNA expression was greatly reduced in C4‐2 xenografts and greatly elevated in PC‐3 xenografts compared with the corresponding cultured cells. NTSR1 mRNA expression was greatly elevated in LNCaP and PC‐3 xenografts. PSCA mRNA expression was elevated in C4‐2 xenografts when compared with C4‐2 cells cultured in vitro. Furthermore, at the protein level, PSCA was re‐expressed in all xenografts compared with cells in culture. CONCLUSIONS The regulation of mRNA and protein expression of the cell‐surface target proteins α ν β 3 , NTSR1, PSMA, and PSCA, in prostate cancer cells with different tumorigenic potential, was influenced by factors of the microenvironment, differing between cell cultures and murine xenotransplants. Integrin α ν β 3 , NTRS1 and PSCA mRNA expression increased with tumorigenic potential, but mRNA expression levels for these proteins do not translate directly to equivalent expression levels of membrane bound protein. Prostate 72:523–532, 2012. © 2011 Wiley Periodicals, Inc.