TY - JOUR
T1 - Integrins and bone metastasis
T2 - Integrating tumor cell and stromal cell interactions
AU - Schneider, Jochen G.
AU - Amend, Sarah R.
AU - Weilbaecher, Katherine N.
N1 - Funding Information:
The authors sincerely thank Dr. Michael Tomasson for his help, guidance and critical reading of this manuscript. This work was supported by the NIH - NIHR0152152 to KNW and by the St. Louis Men's group against cancer (SRA). JGS was supported by an IZKF start up grant from the University of Wuerzburg, Germany . SRA was also supported by the Lucille P. Markey Special Emphasis Pathway in Human Pathobiology at Washington University School of Medicine.
PY - 2011/1/1
Y1 - 2011/1/1
N2 - Integrins on both tumor cells and the supporting host stromal cells in bone (osteoclasts, new blood vessels, inflammatory cells, platelets and bone marrow stromal cells) play key roles in enhancing bone metastasis. Tumor cells localize to specific tissues through integrin-mediated contacts with extracellular matrix and stromal cells. Integrin expression and signaling are perturbed in cancer cells, allowing them to "escape" from cell-cell and cell-matrix tethers, invade, migrate and colonize within new tissues and matrices. Integrin signaling through αvβ3 and VLA-4 on tumor cells can promote tumor metastasis to and proliferation in the bone microenvironment. Osteoclast (OC) mediated bone resorption is a critical component of bone metastasis and can promote tumor growth in bone and αvβ3 integrins are critical to OC function and development. Tumors in the bone microenvironment can recruit new blood vessel formation, platelets, pro-tumor immune cells and bone marrow stromal cells that promote tumor growth and invasion in bone. Integrins and their ligands play critical roles in platelet aggregation (αvβ3 and αIIbβ3), hematopoietic cell mobilization (VLA-4 and osteopontin), neoangiogenesis (αvβ3, αvβ5, α6β4, and β1 integrin) and stromal function (osteopontin and VLA-4). Integrins are involved in the pathogenesis of bone metastasis at many levels and further study to define integrin dysregulation by cancer will yield new therapeutic targets for the prevention and treatment of bone metastasis.
AB - Integrins on both tumor cells and the supporting host stromal cells in bone (osteoclasts, new blood vessels, inflammatory cells, platelets and bone marrow stromal cells) play key roles in enhancing bone metastasis. Tumor cells localize to specific tissues through integrin-mediated contacts with extracellular matrix and stromal cells. Integrin expression and signaling are perturbed in cancer cells, allowing them to "escape" from cell-cell and cell-matrix tethers, invade, migrate and colonize within new tissues and matrices. Integrin signaling through αvβ3 and VLA-4 on tumor cells can promote tumor metastasis to and proliferation in the bone microenvironment. Osteoclast (OC) mediated bone resorption is a critical component of bone metastasis and can promote tumor growth in bone and αvβ3 integrins are critical to OC function and development. Tumors in the bone microenvironment can recruit new blood vessel formation, platelets, pro-tumor immune cells and bone marrow stromal cells that promote tumor growth and invasion in bone. Integrins and their ligands play critical roles in platelet aggregation (αvβ3 and αIIbβ3), hematopoietic cell mobilization (VLA-4 and osteopontin), neoangiogenesis (αvβ3, αvβ5, α6β4, and β1 integrin) and stromal function (osteopontin and VLA-4). Integrins are involved in the pathogenesis of bone metastasis at many levels and further study to define integrin dysregulation by cancer will yield new therapeutic targets for the prevention and treatment of bone metastasis.
KW - Bone metastasis
KW - Cancer therapy
KW - Endothelium
KW - Integrins
KW - Osteoclasts
KW - Platelets
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U2 - 10.1016/j.bone.2010.09.016
DO - 10.1016/j.bone.2010.09.016
M3 - Review article
C2 - 20850578
AN - SCOPUS:78650304364
SN - 8756-3282
VL - 48
SP - 54
EP - 65
JO - Bone
JF - Bone
IS - 1
ER -