Abstract
Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C-terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells.
Highlights
Prostate cancer most frequently develops in men over the age of fifty and is responsible for the second greatest number of deaths in this age group second only to lung cancer [1]
We determined whether at least two different domains of vimentin could be displayed on the surface of these metastatic lines as dual targeting of closely associated epitopes could be utilized for possible improvements of targeted immunotherapy
This polarized localization pattern of surface vimentin has been previously reported on HeLa, HT-29 and HuT-78 cells [8,22,23]
Summary
Prostate cancer most frequently develops in men over the age of fifty and is responsible for the second greatest number of deaths in this age group second only to lung cancer [1]. When prostate cancers are found early enough while still localized within the prostatic capsule, the disease can be cured by radical prostactectomy [2] If this cancer has metastasized beyond the local prostate gland, no curative therapy currently exists and the disease can be lethal [3]. Under these conditions, death typically occurs due to the preferential abilities of certain cancer cells to metastasize to lymph nodes and bone or, in fewer instances, to the brain. With regard to prostate cancer metastases, steps along the pathway to malignant transformation must first occur to produce the life-threatening cell types. If a protein structure could be identified that has a relationship to this common metastatic pathway, its targeting could provide a manner by which to treat currently incurable metastatic disease
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