Tumor Cell-Derived Exosomes from the Prostate Cancer Cell Line TRAMP-C1 Impair Osteoclast Formation and Differentiation.
Skeletal metastatic disease is a deleterious consequence of dissemination of tumor cells from numerous primary sites, such as prostate, lung and breast. Skeletal metastases are still incurable, resulting in development of clinical complications and decreased survival for cancer patients with metastatic disease. During the last decade, tumor cell-derived microvesicles have been identified and suggested to be involved in cancer disease progression. Whether cancer exosomes are involved in tumor and bone cell interactions in the metastatic site is still, however, a rather unexplored field. Here we show that exosomes isolated from the murine prostate cancer cell line TRAMP-C1 dramatically decrease fusion and differentiation of monocytic osteoclast precursors to mature, multinucleated osteoclasts. The presence of tumor 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. In contrast, exosomes derived from murine fibroblastic cells did not affect osteoclast formation. Our findings suggest that exosomes released from tumor cells in the tumor-bone interface are involved in pathological regulation of bone cell formation in the metastatic site. This further strengthens the role of tumor cell-derived microvesicles in cancer progression and disease aggressiveness.
Department of Radiation Sciences, Division of Oncology, Umeå University, Umeå, Sweden.
Terese
T
Karlsson
Department of Medical Biosciences, Division of Pathology, Umeå University, Umeå, Sweden.
Marie
M
Lundholm
Department of Radiation Sciences, Division of Oncology, Umeå University, Umeå, Sweden.
Anders
A
Widmark
Department of Radiation Sciences, Division of Oncology, Umeå University, Umeå, Sweden.
Emma
http://orcid.org/0000-0003-4020-1694
E
Persson
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D055354:Exosomes / Q000473:pathology*; D008297:Male; D051379:Mice; D010010:Osteoclasts / Q000473:pathology*; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D000067996:RAW 264.7 Cells; D013234:Stem Cells / Q000473:pathology*