Limits...
Role of RANKL-induced osteoclast formation and MMP-dependent matrix degradation in bone destruction by breast cancer metastasis.

Ohshiba T, Miyaura C, Inada M, Ito A - Br. J. Cancer (2003)

Bottom Line: The separation of MDA-231 from the calvaria using filter insert showed decreased bone resorption, suggesting that cell-to-cell interaction is essential for cancer-induced bone resorption.Adding MDA-231 cells to bone marrow cultures markedly induced osteoclast formation, and the expression of RANKL in osteoblasts was enhanced by contact with the cell surface of MDA-231 cells.These results indicate that RANKL-induced osteoclast formation and MMP-dependent matrix degradation are associated with osteolysis because of bone metastasis of breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.

ABSTRACT
Bone metastasis of breast cancer induces severe osteolysis with increased bone resorption. Osteoclast differentiation regulated by the receptor activator of NF-kappaB ligand (RANKL) in osteoblasts and matrix degradation induced by matrix metalloproteinases (MMPs) are thought to be involved in the process of bone resorption. When nude mice were inoculated with human breast cancer cells, MDA-MB-231(MDA-231), numerous osteoclasts resorbed bone and the degradation of the bone matrix markedly progressed in the femur and tibia with metastasis of the MDA-231 tumour. The expression of RANKL, MMP-13 and membrane-type 1-MMP mRNA was markedly elevated in bone with metastasis. When MDA-231 cells were cocultured with mouse calvaria, MDA-231 markedly induced bone resorption measured by calcium release from the calvaria, and the expression of RANKL, MMP-2 and MMP-13 was elevated in the calvaria after the coculture. The separation of MDA-231 from the calvaria using filter insert showed decreased bone resorption, suggesting that cell-to-cell interaction is essential for cancer-induced bone resorption. Adding MDA-231 cells to bone marrow cultures markedly induced osteoclast formation, and the expression of RANKL in osteoblasts was enhanced by contact with the cell surface of MDA-231 cells. These results indicate that RANKL-induced osteoclast formation and MMP-dependent matrix degradation are associated with osteolysis because of bone metastasis of breast cancer.

Show MeSH

Related in: MedlinePlus

Expression of RANKL, cathepsin K, TRAP, MMP-13 and MT1-MMP mRNA in bone with metastasis of MDA-231 breast cancer. (A) Nude mice were injected with or without MDA-231 cells and the hindlimbs were subjected to soft X-ray analyses. Arrowheads indicate the osteolytic lesions because of metastasis in the femur and tibia. Mouse A is control mouse without injection of MDA-231 cells. Mouse B possesses slight metastasis in the tibia and severe metastasis in the femur. Mouse C possesses severe metastasis in both the femur and tibia. (B) Total RNA was collected from the femur and tibia shown in panel A, and mRNA expression of RANKL, cathepsin K and TRAP was analysed by RT–PCR. (C) Expression of MMP-13 and MT1-MMP mRNAs was analysed by Northern blotting using total RNA used in panel B. Note that marked expression of RANKL, cathepsin K, TRAP, MMP-13 and MT1-MMP mRNAs was detected only in bone with severe osteolysis because of bone metastasis.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2747560&req=5

fig2: Expression of RANKL, cathepsin K, TRAP, MMP-13 and MT1-MMP mRNA in bone with metastasis of MDA-231 breast cancer. (A) Nude mice were injected with or without MDA-231 cells and the hindlimbs were subjected to soft X-ray analyses. Arrowheads indicate the osteolytic lesions because of metastasis in the femur and tibia. Mouse A is control mouse without injection of MDA-231 cells. Mouse B possesses slight metastasis in the tibia and severe metastasis in the femur. Mouse C possesses severe metastasis in both the femur and tibia. (B) Total RNA was collected from the femur and tibia shown in panel A, and mRNA expression of RANKL, cathepsin K and TRAP was analysed by RT–PCR. (C) Expression of MMP-13 and MT1-MMP mRNAs was analysed by Northern blotting using total RNA used in panel B. Note that marked expression of RANKL, cathepsin K, TRAP, MMP-13 and MT1-MMP mRNAs was detected only in bone with severe osteolysis because of bone metastasis.

Mentions: Using the model of bone metastasis of MDA-231 cells, we examined the expression of RANKL and MMPs in bone with metastasis. Figure 2AFigure 2


Role of RANKL-induced osteoclast formation and MMP-dependent matrix degradation in bone destruction by breast cancer metastasis.

Ohshiba T, Miyaura C, Inada M, Ito A - Br. J. Cancer (2003)

Expression of RANKL, cathepsin K, TRAP, MMP-13 and MT1-MMP mRNA in bone with metastasis of MDA-231 breast cancer. (A) Nude mice were injected with or without MDA-231 cells and the hindlimbs were subjected to soft X-ray analyses. Arrowheads indicate the osteolytic lesions because of metastasis in the femur and tibia. Mouse A is control mouse without injection of MDA-231 cells. Mouse B possesses slight metastasis in the tibia and severe metastasis in the femur. Mouse C possesses severe metastasis in both the femur and tibia. (B) Total RNA was collected from the femur and tibia shown in panel A, and mRNA expression of RANKL, cathepsin K and TRAP was analysed by RT–PCR. (C) Expression of MMP-13 and MT1-MMP mRNAs was analysed by Northern blotting using total RNA used in panel B. Note that marked expression of RANKL, cathepsin K, TRAP, MMP-13 and MT1-MMP mRNAs was detected only in bone with severe osteolysis because of bone metastasis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747560&req=5

fig2: Expression of RANKL, cathepsin K, TRAP, MMP-13 and MT1-MMP mRNA in bone with metastasis of MDA-231 breast cancer. (A) Nude mice were injected with or without MDA-231 cells and the hindlimbs were subjected to soft X-ray analyses. Arrowheads indicate the osteolytic lesions because of metastasis in the femur and tibia. Mouse A is control mouse without injection of MDA-231 cells. Mouse B possesses slight metastasis in the tibia and severe metastasis in the femur. Mouse C possesses severe metastasis in both the femur and tibia. (B) Total RNA was collected from the femur and tibia shown in panel A, and mRNA expression of RANKL, cathepsin K and TRAP was analysed by RT–PCR. (C) Expression of MMP-13 and MT1-MMP mRNAs was analysed by Northern blotting using total RNA used in panel B. Note that marked expression of RANKL, cathepsin K, TRAP, MMP-13 and MT1-MMP mRNAs was detected only in bone with severe osteolysis because of bone metastasis.
Mentions: Using the model of bone metastasis of MDA-231 cells, we examined the expression of RANKL and MMPs in bone with metastasis. Figure 2AFigure 2

Bottom Line: The separation of MDA-231 from the calvaria using filter insert showed decreased bone resorption, suggesting that cell-to-cell interaction is essential for cancer-induced bone resorption.Adding MDA-231 cells to bone marrow cultures markedly induced osteoclast formation, and the expression of RANKL in osteoblasts was enhanced by contact with the cell surface of MDA-231 cells.These results indicate that RANKL-induced osteoclast formation and MMP-dependent matrix degradation are associated with osteolysis because of bone metastasis of breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.

ABSTRACT
Bone metastasis of breast cancer induces severe osteolysis with increased bone resorption. Osteoclast differentiation regulated by the receptor activator of NF-kappaB ligand (RANKL) in osteoblasts and matrix degradation induced by matrix metalloproteinases (MMPs) are thought to be involved in the process of bone resorption. When nude mice were inoculated with human breast cancer cells, MDA-MB-231(MDA-231), numerous osteoclasts resorbed bone and the degradation of the bone matrix markedly progressed in the femur and tibia with metastasis of the MDA-231 tumour. The expression of RANKL, MMP-13 and membrane-type 1-MMP mRNA was markedly elevated in bone with metastasis. When MDA-231 cells were cocultured with mouse calvaria, MDA-231 markedly induced bone resorption measured by calcium release from the calvaria, and the expression of RANKL, MMP-2 and MMP-13 was elevated in the calvaria after the coculture. The separation of MDA-231 from the calvaria using filter insert showed decreased bone resorption, suggesting that cell-to-cell interaction is essential for cancer-induced bone resorption. Adding MDA-231 cells to bone marrow cultures markedly induced osteoclast formation, and the expression of RANKL in osteoblasts was enhanced by contact with the cell surface of MDA-231 cells. These results indicate that RANKL-induced osteoclast formation and MMP-dependent matrix degradation are associated with osteolysis because of bone metastasis of breast cancer.

Show MeSH
Related in: MedlinePlus