Proteomics in investigation of cancer metastasis: functional and clinical consequences and methodological challenges.

Metastases are responsible for most of the cases of death in patients with solid tumors. There is thus an urgent clinical need of better understanding the exact molecular mechanisms and finding novel therapeutics targets and biomarkers of metastatic disease of various tumors. Metastases are formed in a complicated biological process called metastatic cascade.

Identification and characterisation of pro-metastatic targets, pathways and molecular complexes using a toolbox of proteomic technologies.

Background: Cancer metastasis involves changes in signalling pathways, cell adhesion, migration and invasiveness. Modern proteomic, mass spectrometry based techniques enable discovery of new pro-metastatic proteins and their functional partners. Also, they might be involved in their functional characterisation and validation towards development of new diagnostic and therapeutic approaches.

The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo.

Background: The initial pharmacokinetic study of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12) was complemented by proteomic screening of rat plasma. The objective of the study was to identify new LA-12 target proteins that serve as markers of LA-12 treatment, response and therapy monitoring.

Methods: Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) in 72 samples of rat plasma randomized according to LA-12 dose and time from administration.

Fe/Mn superoxide dismutase-encoding gene in Paracoccus denitrificans is induced by azide and expressed independently of the FNR-type regulators.

Paracoccus denitrificans cells undergo changes in protein composition upon exposure to azide, a known activator of the fumarate-nitrate reduction (FNR)-type transcription factor NarR. One of the most prominent protein species inducible by azide is a Fe/Mn-family superoxide dismutase (SOD). Azide induces SOD at protein, mRNA transcript, and enzyme activity levels in the aerobically growing cells.

Unraveling an FNR based regulatory circuit in Paracoccus denitrificans using a proteomics-based approach.

The switch from aerobic to anaerobic respiration in the bacterium Paracoccus denitrificans is orchestrated by the action of three FNR-type transcription regulators FnrP, NNR and NarR, which are sensors for oxygen, nitric oxide and nitrite, respectively. In this work, we analyzed the protein composition of four strains (wild type, FnrP-, NNR- and NarR-mutant strains) grown aerobically, semiaerobically and semiaerobically in the presence of nitrate to discover the global role of FNR-family transcription regulators using proteomics, with data validation at the transcript and genome levels. Expression profiles were acquired using two-dimensional gel electrophoresis for 737 protein spots, in which 640 proteins were identified using mass spectrometry.