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Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway
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Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway
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Journal Article
Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway
2008
Overview
Transforming growth factor (TGF)-β is known to promote tumor invasion and metastasis. Although bone morphogenetic proteins (BMPs), members of the TGF-β family, are expressed in a variety of human carcinoma cell lines, their roles in tumor progression have not been fully clarified. In this study, we sought to determine the roles of BMPs in the progression of breast cancer bone metastasis using human breast cancer samples and a mouse xenograft model. Immunohistochemical analysis of samples from breast cancer patients as well as a mouse xenograft model of MDA-231-D, highly metastatic human breast cancer cells, revealed phospho-Smad2 and phospho-Smad1/5/8 staining in the nuclei of cancer cells in primary tumor and/or bone metastasis. Using a functional
in vivo
bioluminescence imaging system, we showed that TGF-β- and BMP-induced transcriptional pathways are active in bone metastatic lesions
in vivo
. In addition, both TGF-β3 and BMP-2 promoted the motility and invasiveness of the MDA-231-D cells
in vitro
. Moreover, expression of dominant-negative receptors for TGF-β and/or BMPs in the MDA-231-D cells inhibited invasiveness
in vitro
and bone metastasis in the xenograft model. These results suggest that BMPs as well as TGF-β promote invasion and bone metastasis of breast cancer.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Biological and medical sciences
/ Bone morphogenetic protein 2
/ Bone Morphogenetic Proteins - metabolism
/ Bones
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
/ Cellular signal transduction
/ Complications and side effects
/ Diseases of the osteoarticular system
/ Female
/ Fundamental and applied biological sciences. Psychology
/ Genetics
/ Gynecology. Andrology. Obstetrics
/ Humans
/ Medicine
/ Mice
/ Molecular and cellular biology
/ Neoplasm Invasiveness - pathology
/ Oncology
/ Transforming growth factor-b
/ Tumors
/ Tumors of striated muscle and skeleton
