Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer.

Objective: Cancer immunology is a growing field of research whose aim is to develop innovative therapies and diagnostic tests. Starting from the hypothesis that immune cells promptly respond to harmful stimuli, we used peripheral blood monocytes in order to characterise a distinct gene expression profile and to evaluate its potential as a candidate diagnostic biomarker in patients with colorectal cancer (CRC), a still unmet clinical need.

Design: We performed a case-control study including 360 peripheral blood monocyte samples from four European oncological centres and defined a gene expression profile specific to CRC.

Mapping of binding site III in the leptin receptor and modeling of a hexameric leptin.leptin receptor complex.

The leptin.leptin receptor (LR) system shows strong similarities to the long chain cytokine interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) cytokine.cytokine receptor systems.

Mapping of the interface between leptin and the leptin receptor CRH2 domain.

Despite the impact of the leptin system on body weight and other physiologic processes, little is known about the binding of leptin to its receptor. The extracellular domain of the leptin receptor consists of two cytokine receptor homology (CRH) domains separated by an immunoglobulin-like domain, and followed by two juxtamembrane fibronectin type III modules. The CRH2 domain functions as a high-affinity binding site for leptin, and we previously demonstrated interaction with helices A and C of leptin.

Leptin receptor activation depends on critical cysteine residues in its fibronectin type III subdomains.

The leptin receptor (LR) complex is composed of a single subunit belonging to the class I cytokine receptor family and exists as a preformed complex. The extracellular portion contains two cytokine receptor homology (CRH) domains, separated by an Ig-like domain and followed by two membrane-proximal fibronectin type III (FNIII) domains. The mechanisms underlying ligand-induced receptor activation are still poorly understood.

Mapping of the leptin binding sites and design of a leptin antagonist.

The leptin/leptin receptor system shows strong similarities to the long-chain cytokine interleukin-6 (IL-6) and granulocyte colony-stimulating factor cytokine/receptor systems. The IL-6 family cytokines interact with their receptors through three different binding sites I-III. The leptin structure was superposed on the crystal structures of several long-chain cytokines, and a series of leptin mutants was generated focusing on binding sites I-III.

Functional analysis of leptin receptor activation using a Janus kinase/signal transducer and activator of transcription complementation assay.

The leptin receptor (LR), a member of the class I cytokine receptor family, is composed of a single subunit. Its extracellular domain consists of two so-called cytokine receptor homology domains, separated by an Ig-like domain, and two additional fibronectin type III modules. Requirements for LR activation were examined using a complementation strategy.