Inhibition of stimulated bone resorption in vitro by TIMP-1 and TIMP-2

Hill, Peter A.; Reynolds, John J.; Meikle, Murray C.

doi:10.1016/0167-4889(93)90159-m

Cited by 70 publications

(48 citation statements)

References 19 publications

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“…Immunohistochemical study using clinical materials revealed prominent expression of MMP-9 (gelatinase B) in cancer cells housed in bone (39). Furthermore, recent studies showed that MMP-9 (gelatinase B) was involved in the stimulation of bone resorption by parathyroid hormone (40), and that the recombinant TIMP-1 and TIMP-2 inhibited bone resorption (41). Taken together, it is plausible to speculate that MMPs play a role not only in the common steps but also in the specific step of osteoclastic bone destruction in breast cancer metastasis to bone.…”

Section: Discussionmentioning

confidence: 98%

Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2.

et al. 1997

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Multiple steps are involved in the metastasis of cancer cells from primary sites to distant organs. These steps should be considered in the design of pharmacologic approaches to prevent or inhibit the metastatic process. In the present study, we have compared the effects of inhibiting several steps involved in the bone metastatic process individually with inhibition of both together. The steps we chose were matrix metalloproteinase (MMP) secretion, likely involved in tumor cell invasion, and osteoclastic bone resorption, the final step in the process. We used an experimental model in which inoculation of human estrogen-independent breast cancer MDA-231 cells into the left cardiac ventricle of female nude mice causes osteolytic lesions in bone. To inhibit cancer invasiveness, the tissue inhibitor of the MMP-2 (TIMP-2), which is a natural inhibitor of MMPs, was over-

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Section: Discussionmentioning

confidence: 98%

Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2.

et al. 1997

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“…Yoneda et al (1997) have reported that osteolytic bone metastasis of breast cancer could be inhibited by combined treatment with bisphosphonate, a specific inhibitor of osteoclastic bone resorption, and tissue inhibitor of MMP (TIMP)-2, a natural inhibitor of MMPs. Since previous studies have shown that recombinant TIMP-1 and TIMP-2 inhibited bone resorption in vitro (Hill et al, 1993), TIMP-2 may suppress bone metastasis by inhibiting both tumour invasion and bone resorption.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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Bone metastasis of breast cancer induces severe osteolysis with increased bone resorption. Osteoclast differentiation regulated by the receptor activator of NF-kB 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.

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“…Both TIMP genes are expressed in normal glomeruli, and their expression is increased in glomerulosclerosis associated with renal carcinoma [29]. Furthermore, endogenous TIMPs play a central role in regulating both physiological and pathological bone resorption [37].…”

Section: S 18smentioning

confidence: 99%

Tissue inhibitor of metalloproteinases‐2 (TIMP‐2) in rat liver cells is increased by lipopolysaccharide and prostaglandin E₂

Roeb¹,

Rose-John²,

Erren³

et al. 1995

FEBS Letters

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To explore the functional role of TIMP-2 in liver, we determined TIMP-2 mRNA levels in primary rat hepatocytes and in total rat liver. Rat hepatocytes constitutively express TIMP-2 mRNA at a low level. Incubation with dexamethasone, prostaglandin E2 and a combination of inflammatory cytokines leads to an up-regulation of TIMP-2 mRNA. In rats in vivo we found a dramatic increase of TIMP-2 expression after intraperitoneal injection of lipopolysaccharide. Compared to our previous findings on TIMP-1 we conclude that TIMP-2 mRNA expression is regulated in a distinct and partially opposite manner. Over-production of TIMP-2 could inhibit the activity of metalloproteinases and thus lead to matrix accumulation. Dysregulation of TIMP-2 synthesis might be involved in the development of liver fibrosis.

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Inhibition of stimulated bone resorption in vitro by TIMP-1 and TIMP-2

Cited by 70 publications

References 19 publications

Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2.

Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2.

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

Tissue inhibitor of metalloproteinases‐2 (TIMP‐2) in rat liver cells is increased by lipopolysaccharide and prostaglandin E₂

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Inhibition of stimulated bone resorption in vitro by TIMP-1 and TIMP-2

Cited by 70 publications

References 19 publications

Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2.

Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2.

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

Tissue inhibitor of metalloproteinases‐2 (TIMP‐2) in rat liver cells is increased by lipopolysaccharide and prostaglandin E2

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Tissue inhibitor of metalloproteinases‐2 (TIMP‐2) in rat liver cells is increased by lipopolysaccharide and prostaglandin E₂