Platelets govern pre-metastatic tumor communication to bone.
Although the survival rate for early detected cancers is high, once a cancer metastasizes to bone, it is incurable. Interestingly, patients without visible metastases display abnormal bone formation and resorption, suggesting a link between primary cancers and the bone microenvironment prior to metastasis, and this link likely facilitates preparation of the pre-metastatic niche. We hypothesized that communication with the primary tumor would result in bone remodeling alterations, and that platelets could facilitate this communication. By using three tumor models, we demonstrate that primary tumor growth stimulates bone formation measured by microcomputed tomography. Further, platelet depletion prevented tumor-induced bone formation, highlighting the importance of platelets in the communication between tumors and the bone microenvironment. Finally, we determine that platelets sequester a variety of tumor-derived proteins, TGF-β1 and MMP-1 in particular, which regulate bone formation. Thus, our data reveal that platelets function as mediators of tumor-bone communication prior to metastasis.
Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH, USA.
B A
BA
Kerr
N P
NP
McCabe
W
W
Feng
T V
TV
Byzova
D000469:Alkaline Phosphatase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000556:secondary*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000473:pathology*; D015675:Osteocalcin / Q000097:blood / Q000378:metabolism; D010012:Osteogenesis; D011859:Radiography; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014183:Transplantation, Heterologous
D053773:Transforming Growth Factor beta1; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D020782:Matrix Metalloproteinases