Anti-DDR2 (aa 277-377) polyclonal antibody

Prostate cancer frequently metastasizes to the skeleton but the underlying mechanism remains largely undefined. Discoidin domain receptor 2 (DDR2) is a member of receptor tyrosine kinase (RTK) family and is activated by collagen binding. This study aimed to investigate the function and detailed mechanism of DDR2 in prostate cancer bone dissemination. Herein we found that DDR2 was strongly expressed in bone-metastatic prostate cancer cells and tissues compared to that in normal controls. Enhanced expression of constitutively activated DDR2 led to elevation in motility and invasiveness of prostate cancer cells, whereas knockdown of DDR2 through specific shRNA caused a dramatic repression. Knockdown of DDR2 in prostate cancer cells resulted in significant decrease in the proliferation, differentiation and function of osteoblast Over-expression of DDR2 in prostate cancer cells resulted in notable acceleration of osteoclast differentiation and bone resorption, whereas knockdown of DDR2 exhibited the opposite effects. An intrabone injection bone metastasis animal model demonstrated that DDR2 promoted osteolytic metastasis in vivo. Molecular evidence demonstrated that DDR2 regulated the expression, secretion, and promoter activity of parathyroid hormone-related protein (PTHrP), via modulating Runx2 phosphorylation and transactivity. DDR2 was responsive to TGF-beta and involved in TGF-beta-mediated osteoclast activation and bone resorption. In addition, DDR2 facilitated prostate cancer cells adhere to type I collagen. This study reveals for the first time that DDR2 plays an essential role in prostate cancer bone metastasis. The mechanism disclosure may provide therapeutic targets for the treatment of prostate cancer. (C) 2014 Elsevier B.V. All rights reserved.

Squamous-cell carcinomas of the lung (SQCLCs) are defined by unique clinicopathological and molecular characteristics that have evolved substantially over time. Historically, these neoplasms were the most common subtype of non-small-cell lung cancers and were regarded as central tumours with high molecular complexity without targetable genetic abnormalities. Today, the incidence of SQCLCs is surpassed by adenocarcinomas of the lung with a shift towards peripheral squamous tumours. Differential responses to cytotoxic and biological treatments have reshaped our approach to standard therapies. Additionally, evidence of unique biology has emerged with the discovery of SOX2 amplification, NFE2L2 and KEAP1 mutations, PI3K pathway changes, FGFR1 amplification, and DDR2 mutations. These discoveries have ushered in a new era of targeted therapeutic agents for patients with this disease. This Review draws attention to the distinct clinical and pathological characteristics of SQCLCs, summarises present experience with existing cytotoxic and targeted therapies, and discusses emerging treatments based on new insights into the biology of this disease.