Platelets govern pre-metastatic tumor communication to bone

Oncogene. 2013 Sep 5;32(36):4319-24. doi: 10.1038/onc.2012.447. Epub 2013 Sep 15.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alkaline Phosphatase / blood
  • Alkaline Phosphatase / metabolism
  • Animals
  • Blood Platelets / metabolism*
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / secondary*
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Models, Animal
  • Humans
  • Male
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Neoplasms / pathology*
  • Osteocalcin / blood
  • Osteocalcin / metabolism
  • Osteogenesis
  • Radiography
  • Transforming Growth Factor beta1 / metabolism
  • Transplantation, Heterologous

Substances

  • Transforming Growth Factor beta1
  • Osteocalcin
  • Alkaline Phosphatase
  • Matrix Metalloproteinases