Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0153690 (
bone metastases
)
6,382
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Treatment of
bone metastases
is largely symptomatic and is still an unmet medical need. Current therapies mainly target the late phase of tumor-induced osteoclast activation and hereby inhibit further metastatic growth. This treatment method is, however, less effective in preventing initial tumor engraftment, a process that is supposed to depend on the bone microenvironment. We explored whether bone-derived
placental growth factor
(
PlGF
), a homologue of vascular endothelial growth factor-A, regulates osteolytic metastasis. Osteogenic cells secrete
PlGF
, the expression of which is enhanced by bone-metastasizing breast tumor cells. Selective neutralization of host-derived
PlGF
by anti-mouse
PlGF
(alphaPlGF) reduced the incidence, number, and size of
bone metastases
, and preserved bone mass. alphaPlGF did not affect metastatic tumor angiogenesis but inhibited osteoclast formation by preventing the upregulation of the osteoclastogenic cytokine receptor activator of NF-kappaB ligand in osteogenic cells, as well as by blocking the autocrine osteoclastogenic activity of
PlGF
. alphaPlGF also reduced the engraftment of tumor cells in the bone and inhibited their interaction with matrix components in the metastatic niche. alphaPlGF therefore inhibits not only the progression of metastasis but also the settlement of tumor in the bone. These findings identify novel properties of
PlGF
and suggest that alphaPlGF might offer opportunities for adjuvant therapy of bone metastasis.
...
PMID:Anti-placental growth factor reduces bone metastasis by blocking tumor cell engraftment and osteoclast differentiation. 2068 98
