VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors.
Standard
VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors. / Lu, Xin; Mu, Euphemia; Wei, Yong; Riethdorf, Sabine; Yang, Qifeng; Yuan, Min; Yan, Jun; Hua, Yuling; Tiede, Benjamin J; Lu, Xuemin; Haffty, Bruce G; Pantel, Klaus; Massagué, Joan; Kang, Yibin.
In: CANCER CELL, Vol. 20, No. 6, 6, 2011, p. 701-714.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors.
AU - Lu, Xin
AU - Mu, Euphemia
AU - Wei, Yong
AU - Riethdorf, Sabine
AU - Yang, Qifeng
AU - Yuan, Min
AU - Yan, Jun
AU - Hua, Yuling
AU - Tiede, Benjamin J
AU - Lu, Xuemin
AU - Haffty, Bruce G
AU - Pantel, Klaus
AU - Massagué, Joan
AU - Kang, Yibin
PY - 2011
Y1 - 2011
N2 - Breast cancer patients often develop locoregional or distant recurrence years after mastectomy. Understanding the mechanism of metastatic recurrence after dormancy is crucial for improving the cure rate for breast cancer. Here, we characterize a bone metastasis dormancy model to show that aberrant expression of vascular cell adhesion molecule 1 (VCAM-1), in part dependent on the activity of the NF-?B pathway, promotes the transition from indolent micrometastasis to overt metastasis. By interacting with the cognate receptor integrin ?4?1, VCAM-1 recruits monocytic osteoclast progenitors and elevates local osteoclast activity. Antibodies against VCAM-1 and integrin ?4 effectively inhibit bone metastasis progression and preserve bone structure. These findings establish VCAM-1 as a promising target for the prevention and inhibition of metastatic recurrence in bone.
AB - Breast cancer patients often develop locoregional or distant recurrence years after mastectomy. Understanding the mechanism of metastatic recurrence after dormancy is crucial for improving the cure rate for breast cancer. Here, we characterize a bone metastasis dormancy model to show that aberrant expression of vascular cell adhesion molecule 1 (VCAM-1), in part dependent on the activity of the NF-?B pathway, promotes the transition from indolent micrometastasis to overt metastasis. By interacting with the cognate receptor integrin ?4?1, VCAM-1 recruits monocytic osteoclast progenitors and elevates local osteoclast activity. Antibodies against VCAM-1 and integrin ?4 effectively inhibit bone metastasis progression and preserve bone structure. These findings establish VCAM-1 as a promising target for the prevention and inhibition of metastatic recurrence in bone.
KW - Animals
KW - Humans
KW - Female
KW - Mice
KW - Mice, Inbred BALB C
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Cell Differentiation
KW - Cell Adhesion
KW - Antibodies, Monoclonal/therapeutic use
KW - Bone Neoplasms/metabolism/prevention & control/secondary
KW - Breast Neoplasms/metabolism/pathology
KW - Chemotaxis
KW - Integrin alpha4beta1/immunology/metabolism
KW - Mice, Nude
KW - Molecular Targeted Therapy
KW - NF-kappa B/metabolism
KW - Neoplasm Micrometastasis
KW - Neoplasm Transplantation
KW - Osteoclasts/metabolism/pathology
KW - Osteolysis/radiography
KW - Stem Cells/metabolism/pathology
KW - Transplantation, Heterologous
KW - Vascular Cell Adhesion Molecule-1/genetics/immunology/metabolism
KW - Animals
KW - Humans
KW - Female
KW - Mice
KW - Mice, Inbred BALB C
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Cell Differentiation
KW - Cell Adhesion
KW - Antibodies, Monoclonal/therapeutic use
KW - Bone Neoplasms/metabolism/prevention & control/secondary
KW - Breast Neoplasms/metabolism/pathology
KW - Chemotaxis
KW - Integrin alpha4beta1/immunology/metabolism
KW - Mice, Nude
KW - Molecular Targeted Therapy
KW - NF-kappa B/metabolism
KW - Neoplasm Micrometastasis
KW - Neoplasm Transplantation
KW - Osteoclasts/metabolism/pathology
KW - Osteolysis/radiography
KW - Stem Cells/metabolism/pathology
KW - Transplantation, Heterologous
KW - Vascular Cell Adhesion Molecule-1/genetics/immunology/metabolism
M3 - SCORING: Journal article
VL - 20
SP - 701
EP - 714
JO - CANCER CELL
JF - CANCER CELL
SN - 1535-6108
IS - 6
M1 - 6
ER -