Pathogenesis of Bone Metastases: Role of Tumor-Related Proteins

Endothelin-1 regulates rat bone sialoprotein gene transcription

“…BSP and OPN, as members of the family of small integrin-binding proteins (SIBLINGs), are the major constituents of non-collagenous proteins in bone matrix, and expression of their gene products has been shown to be under the control of calcitropic hormones and cytokines (28,53). ET-1 is a key mediator of osteoblastic bone metastasis, which is characteristic of breast and prostate cancers (24,25). In the present study, ET-1 increased the levels of BSP and OPN mRNA and transcriptional activity of the BSP gene ( Fig.…”

“…In pathological situations, tumor-derived ET-1 may induce localized bone formation when certain types of breast and prostate cancer metastasize to bone (24,25). Human breast and prostate cancer cell lines abundantly secrete ET-1.…”

Physiopathology of Spine Metastasis

“…Preferential localization in skeletal segments which contain red bone marrow (vertebral bodies, ribs, iliac bones, the sternum, the femoral head, the epiphysis of long bones) can be explained by the fact that the rich vascularity allows cancer cells to be transported to this level and reduced blood flow velocity [62], together with the formation of vortices and/or microthrombi, promotes the adhesion and immobilization of the tumour cells on the endothelial ones. Another theory suggests that neoplastic cells migrate to and localize in a preferential target tissue because that is where they find the most fertile “soil” in which to grow, because the bone and bone marrow cells contain and express a variety of growth factors, cytokines, enzymes, and hormone-like substances which, together with similar factors produced by cancer cells, can make the bone microenvironment (the “soil”) suitable for cellular implantation (the “seeding”) and development [39, 63–66]. MMPs, BSP, and OPN play a key role in the implantation of neoplastic cells in bone marrow by degrading the extracellular matrix modifying cell-cell and cell-matrix contacts and interactions regulation of attachment and chemotactic migration of endothelial cells, and the promotion of angiogenesis [40, 49, 57, 67, 68].…”

Exome-capture RNA sequencing of decade-old breast cancers and matched decalcified bone metastases

“…Molecular characteristics of ER-positive specimens that have recurred in an estrogen-blunted system, which represents the major burden of breast cancer BoM, are thus essential to reinforce the significant scientific contributions made using in vivo bone metastasis models (6)(7)(8)(9). Nonetheless, data sets are currently limited, in part due to the practical difficulties of obtaining and processing human BoM specimens (10).…”