BONE-NET

European Training Network on Cancer-Induced Bone Diseases

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 Obiettivo del progetto (Objective)

'Several cancers are prone to metastasize to bone. Combating bone metastasis, especially the early dissemination of cancer cells in bone, requires basic research knowledge, skills in different technologies and longstanding clinical experience in order to make clinically significant progress. BONE-NET is a european consortium with complementary expertises in the fields of cancer and bone. It brings together 6 leading academic groups and 3 SMEs. BONE-NET’s scientific project will aim at investigating the early molecular mechanisms of metastases associated with breast and prostate cancers and primary bone cancers (e.g., osteosarcomas), including the identification of new genes and their regulators (microRNAs) that draw cancer cells to colonize bone and let these cells adapt and thrive in the bone marrow. This network will then seek to identify and develop molecularly-targeted therapies. BONE-NET’s primary objective will be to train 11 early-stage (ESR) and 3 experienced (ER) researchers in technical skills such as genomics, proteomics, advanced microscopical methods, animal experimentation, noninvasive in vivo imaging methodologies and drug development. None of the participating laboratories use all of these approaches, but through workshops, courses and secondments ESR/ER will become expert in many of these disciplines. The network additional objective will be to foster collaborations between participating laboratories, in which ESR/ER will take part through individual training-through-research projects. The training programme will also expose the ESR/ER to the industry which will offer courses and a set of complementary skills (ethics, intellectual property rights, entrepreneurship), thereby enabling them to gain industrial work experience. Overall, at the end of the project, ESR/ER will have acquired enough skills in order to manage their own research programmes and to envisage attractive career perspectives within Europe.'

Introduzione (Teaser)

BONE-NET, an EU-funded project, aims to train 10 early-stage researchers (ESRs) and 4 experienced researchers (ERs) in technical skills. The expertise gained will include areas such as genomics, proteomics, advanced microscopical methods, animal experimentation, non-invasive in vivo imaging methodologies and drug development.

Descrizione progetto (Article)

The 'European training network on cancer-induced bone diseases' (BONE-NET) consortium includes seven leading academic groups and two small and medium-sized enterprises (SMEs). Their members will research cancer-induced bone diseases by investigating early molecular mechanisms to identify genetic factors associated with cancer metastasis. In addition, researchers will work on developing new molecularly targeted therapies and biomarkers for diagnosis.

Recruitment of talented ESRs and ERs was done by publishing open positions on BONE-NET and EURAXESS websites. To date, 10 ESRs and 1 ER have joined the BONE-NET project and the recruitment process is ongoing. Joint training events included courses on proteomics and functional genomics, and a workshop on gene identification and gene therapy.

Project members collected samples from osteosarcoma patients and bone marrow aspirates from prostate or breast cancer patients along with animal model samples. RNA extraction protocols were selected for messenger RNA (mRNA) and microRNA (miRNA) profiling of these samples. Pre-clinical models of bone metastases and osteosarcoma yielded a list of miRNAs that warranted further investigation.

mRNA and miRNA expression profiles of osteotropic human breast and prostate cancer cell lines were successfully generated. Chimerical RNA samples of experimentally induced bone metastasis were sequenced. BONE-NET researchers also performed proteomic profiling of three proteins of interest on osteotropic prostate and breast cancer clones.

In vitro assays were used to elucidate the role of miRNAs in modulating stemness, clonogenicity and epithelial plasticity. Setup of various in vivo cancer models of animals is ongoing. The role of miRNAs on development of skeletal lesions caused by osteosarcoma and carcinomas will be assessed using bone histomorphometry.

BONE-NET members have started preliminary work for researching liposomal drug encapsulation, bone sarcoma therapy and blocking targeted gene expression in cancer suppression.

Successful project outcomes will identify genes and their miRNA regulators involved in cancer metastasis or spread. Studies could also point out cancer patients at higher risk of relapse and assess effectiveness of molecularly oriented therapies that target micrometastases. This would improve health care outcomes by saving or prolonging life and reducing health care costs. Data derived from these studies could also be applicable to other forms of metastatic cancers.

Training initiatives undertaken during the project should harmonise methodologies, and ensuing expertise will increase the competitiveness of participating institutions on a global scale.