期刊
NEOPLASIA
卷 20, 期 2, 页码 140-151出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neo.2017.10.009
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资金
- Deutsche Forschungsgemeinschaft [SCHI 871/5, SCHI 871/6, SCHI 871/8, SCHI 871/9, GR 1748/6, INST 39/900-1, INST 39/935-1, SFB850-Project B8]
- European Research Council [ERC-2011-StG 282111-ProteaSys]
- Excellence Initiative of the German Federal Government [EXC 294, BIOSS]
- Excellence Initiative of the German State Government [EXC 294]
- Integrated Research Training Group of the CRC 850 Control of Cell Motility in Morphogenesis, Cancer Invasion and Metastasis.
Patients with metastatic prostate cancer (PCa) have a poorer prognosis than patients with organ-confined tumors. We strove to uncover the proteome signature of primary PCa and associated lymph node metastases (LNMs) in order to identify proteins that may indicate or potentially promotemetastases formation. We performed a proteomic comparative profiling of PCa tissue from radical prostatectomy (RPE) of patients without nodal metastases or relapse at the time of surgical resection (n = 5) to PCa tissue from RPE of patients who suffered from nodal relapse (n = 5). For the latter group, we also included patient-matched tissue of the nodal metastases. All samples were formalin fixed and paraffin embedded. We identified and quantified more than 1200 proteins by liquid chromatography tandem mass spectrometry with subsequent label-free quantification. An increase of ribosomal or proteasomal proteins in LNM (compared to corresponding PCa) became apparent, while extracellular matrix components rather decreased. Immunohistochemistry (IHC) corroborated accumulation of poly-(ADP-ribose)-polymerase 1 and N-myc-downstream-regulated-gene 3, alpha/beta hydrolase domain-containing protein 11, and protein phosphatase slingshot homolog 3 in LNM. These findings strengthen the present interest in examining PARP inhibitors for the treatment of aggressive PCa. IHC also corroborated increased abundance of retinol dehydrogenase 11 in metastasized primary PCa compared to organ-confined PCa. Generally, metastasizing primary tumors were characterized by an enrichment of proteins involved in cellular lipid metabolic processes with concomitant decrease of cell adhesion proteins. This study highlights the usefulness of a combined proteomic-IHC approach to explore novel aspects in tumor biology. Our initial results open novel opportunities for follow-up studies.
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