Article

Human antibodies targeting cell surface antigens overexpressed by the hormone refractory metastatic prostate cancer cells: ICAM-1 is a tumor antigen that mediates prostate cancer cell invasion

UCSF Helen Diller Family Comprehensive Cancer Center San Francisco CA 94110 USA
Journal of Molecular Medicine (Impact Factor: 4.74). 05/2009; 87(5):507-514. DOI: 10.1007/s00109-009-0446-3
Source: PubMed

ABSTRACT Transition from hormone-sensitive to hormone-refractory metastatic tumor types poses a major challenge for prostate cancer
treatment. Tumor antigens that are differentially expressed during this transition are likely to play important roles in imparting
prostate cancer cells with the ability to grow in a hormone-deprived environment and to metastasize to distal sites such as
the bone and thus, are likely targets for therapeutic intervention. To identify those molecules and particularly cell surface
antigens that accompany this transition, we studied the changes in cell surface antigenic profiles between a hormone-sensitive
prostate cancer line LNCaP and its hormone-refractory derivative C4-2B, using an antibody library-based affinity proteomic
approach. We selected a naïve phage antibody display library to identify human single-chain antibodies that bind specifically
to C4-2B but not LNCaP. Using mass spectrometry, we identified one of the antibody-targeted antigens as the ICAM-1/CD54/human
rhinovirus receptor. Recombinant IgG1 derived from this single-chain antibody binds to a neutralizing epitope of ICAM-1 and
blocks C4-2B cell invasion through extracellular matrix in vitro. ICAM-1 is thus differentially expressed during the transition
of the hormone-sensitive prostate cancer cell line LNCaP to its hormone-refractory derivative C4-2B, plays an important role
in imparting the C4-2B line with the ability to invade, and may therefore be a target for therapeutic intervention.

KeywordsHormone refractory metastatic prostate cancer-Mass spectrometry-LNCaP-C4-2B-ICAM-1/CD54/rhinovirus receptor-Human single-chain antibodies-Neutralizing human IgG

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