ECTS Abstracts (2015) 1 P112

Prostate Cancer Cell-Derived Exosomes Impair Osteoclast Formation and Differentiation

Emma Persson, Terese Karlsson, Marie Lundholm & Anders Widmark

Umea University, UMEA, Sweden.

Skeletal metastatic disease is a deleterious consequence of tumourigenic growth and subsequent dissemination of tumour cells from numerous primary sites, such as prostate, lung and breast. Skeletal metastases are still incurable, resulting in dramatically decreased survival and development of clinical complications such as increased fracture risk, skeletal pain and anaemia for cancer patients with metastatic disease. During the last decade, tumour cell-derived microvesicles have been identified and suggested to be involved in cancer disease progression. Whether cancer exosomes are involved in tumour and bone cell interactions in the metastatic site is still, however, an unexplored field. Here we show that exosomes isolated from prostate cancer cells both decrease proliferation of monocytic osteoclast precursors and clearly impair fusion of osteoclast progenitor cells to mature, multinucleated osteoclasts. Furthermore, the presence of tumour cell-derived exosomes also clearly decreased the expression of established markers for osteoclast fusion and differentiation, including DC-STAMP, TRAP, cathepsin K, and MMP-9. This is, to the best of our knowledge, the first report showing direct effects by tumour cell-derived microvesicles, exosomes, on osteoclast formation and differentiation. Our findings suggest that exosomes released from tumour cells in the tumour-bone interface are involved in the pathological regulation of bone cell formation in the metastatic site. This further strengthens the role of tumour cell-derived microvesicles in prostate cancer progression and disease aggressiveness.

Disclosure: The authors declared no competing interests. This work was supported by the Swedish Cancer Society (grant number CAN 2012/743), and AFA Insurance (grant number 120338).

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