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Bone Abstracts (2016) 5 CABSOP1.1 | DOI: 10.1530/boneabs.5.CABS.OP1.1

1Urology Research Laboratory, Department of Urology and Department of Clinical Research, University of Bern, Bern, Switzerland; 2Tumorimmunology, Department of Clinical Research, University of Bern, Bern, Switzerland; 3Biomedical Informatics Division, Sidra Medical and Research Center, Doha, Qatar; 4Department of Urology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands.


Cancer cell growth is dependent on the microenvironmental support. Prostate and mammary cancer (PCa and MCa) cells preferentially metastasize to bone, where they induce either an osteoblastic or osteolytic response. These opposite stromal responses suggest that different types of cancers adopt distinct strategies to hijack the bone marrow/bone stroma for their growth support. However, the molecular cues underlying these divergent responses are largely elusive.

We exploited the sufficient divergence between human and mouse RNA sequences to dissect the stroma (mouse) from the cancer cell (human) transcriptome in bone xenograft models of human osteoinductive PCa cells and of pro-osteolytic PCa and MCa cells.

The stroma transcriptome of osteoblastic bone metastases (OB-BMet) differs substantially from that of osteolytic bone metastases (OL-BMet). Although, the biological process “angiogenesis/vasculogenesis” dominates in both transcriptomes, the “vascular/axon guidance” process is manifest only in the OL-BMet. Consistently with this, the types of vessels are markedly different between the two types of metastatic lesions. In OB-BMet angiogenesis is characterized by sinusoidal morphology and marker expression of osteogenesis-coupled “H-vessels” that have been associated to the expanding hematopoietic stem cell (HSC) compartment in the marrow. In contrast, in OL-BMet angiogenesis is denoted by vessel morphology and marker expression specific for arterioles. These vessels have been associated with the maintenance of HSC quiescence. Remarkably, the stroma reaction in OL-BMet is also marked by a hyper-recruitment of mesenchymal stem cells/vascular smooth muscle cells, likely to be a major source of pro-osteolytic cytokines and of inhibitors of bone formation. This is also paralleled by intratumoral neurite ingrowth.

In conclusion, osteoinductive and pro-osteolytic cancer cells trigger divergent types of angiogenesis, representing functionally different HSC niches and, thus, different growth support requirements. This may imply the need for a differential anti-angiogenic strategy for interfering with tumour growth in osteoblastic and osteolytic lesions.

Volume 5

43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

European Calcified Tissue Society 

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