Effects of DNA and prostaglandin synthesis inhibitors on the stimulation of bone resorption by epidermal growth factor in fetal rat long-bone cultures.

Lorenzo, Joseph; Quinton, J; Sousa, Sandra L.; Raisz, Lawrence G.

doi:10.1172/jci112517

Cited by 52 publications

(19 citation statements)

References 35 publications

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“…The decreases in bone resorption observed with TGF-3 in fetal rat long bones may therefore be caused by an inhibition of osteoclast precursor proliferation. A comparison between TGF-# 1 and the DNA synthesis inhibitor HU, which effectively inhibits osteoclast proliferation in long bones (18,30), showed that the inhibitory effects of TGF-#3l and HU in long bones were indeed similar in many aspects. Unlike calcitonin, which rapidly inhibits bone resorption by acting on mature osteoclasts (31), HU and TGF-#3l had little effect on bone resorption during the first half of the 6-d incubation period, but both inhibited bone resorption during the second half.…”

Section: Resultsmentioning

confidence: 99%

Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures.

Pfeilschifter¹,

Seyedin²,

Mundy³

1988

J. Clin. Invest.

256

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Section: Resultsmentioning

confidence: 99%

Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures.

Pfeilschifter¹,

Seyedin²,

Mundy³

1988

J. Clin. Invest.

256

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“…Early in vitro studies showed that addition of TGF-a and EGF to bone marrow culture, foetal rat long bone and neonatal mouse calvaria stimulated osteoclast formation and bone resorption (Ibbotson et al, 1986;Lorenzo et al, 1986;Takahashi et al, 1986). Phenotypes from genetically modified mice confirmed the important role of EGF signalling in bone formation.…”

Section: Egf Signalling In Bone Developmentmentioning

confidence: 98%

Epidermal growth factor signalling and bone metastasis

Lü

Kang

2009

Br J Cancer

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Epidermal growth factor (EGF) signalling is well known for its multifaceted functions in development and tissue homoeostasis. The EGF family of ligands and receptors (ERBB family) have also been extensively investigated for their roles in promoting tumourigenesis and metastasis in a variety of cancer types. Recent findings indicate that EGF signalling is an important mediator of bone metastasis in breast, prostate and kidney cancers. The EGF signalling stimulates the growth of bone metastasis directly by increasing tumour cell proliferation and indirectly by engaging bone stromal cell in metastasis-promoting activities. Therefore, molecular targeting of ERBB receptors may benefit patients with bone metastasis and should be evaluated in clinical trials.

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“…EGFR family members have long been known to stimulate bone resorption (Ibbotson et al 1986;Lorenzo et al 1986;Takahashi et al 1986). Recent investigation showed that the increased osteoclastogenesis is due to alterations of osteoblast-expressed RANKL and OPG (Zhu et al 2007), as osteoclasts do not express EGRF.…”

Section: Downstream Effectors Of Mmps: Contributions To Osteolysismentioning

confidence: 99%

“…The differential expression of these EGF family members was not regulated at the mRNA level, as assessed by Northern blot analysis, but rather at the post-translational level. Indeed, ADAMTS1 was shown by others to release membrane-bound EGF-like ligands (Liu et al 2006) and Lu et al (2009) showed that MMP-1 could proteolytically cleave AREG, HB-EGF, and TGF-a.EGFR family members have long been known to stimulate bone resorption (Ibbotson et al 1986;Lorenzo et al 1986;Takahashi et al 1986). Recent investigation showed that the increased osteoclastogenesis is due to alterations of osteoblast-expressed RANKL and OPG (Zhu et al 2007), as osteoclasts do not express EGRF.…”

mentioning

confidence: 99%

Breaking down bone: new insight into site-specific mechanisms of breast cancer osteolysis mediated by metalloproteinases: Figure 1.

Guise

2009

Genes Dev.

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Bone metastases are the most common skeletal complication of malignancy. Tumor cells disrupt normal bone remodeling to promote bone destruction and its associated morbidity. In the August 15, 2009, issue of Genes & Development, Lu and colleagues (pp. 1882-1894) propose a novel molecular mechanism by which tumor-produced metalloproteinases release epidermal growth factor (EGF) ligands to activate the central osteoclastogenic pathway receptor activator of NF-kB ligand (RANKL) to promote breast cancer osteolysis. This work has important therapeutic applications that may quickly translate to more effective treatment for bone metastases.Bone metastases are common in breast, prostate, and lung cancer, and are associated with significant morbidity. Unique aspects of the bone microenvironment-such as mineralized bone matrix, which houses immobilized growth factors, bone-destroying osteoclasts, and boneforming osteoblasts-make it a fertile soil for these cancers to grow. Significant insight into the molecular mechanisms responsible for the proclivity of tumors to metastasize and grow in bone has been gleaned in recent years from mouse models and clinical studies. Bone destruction mediated by solid tumor metastases to bone, particularly in breast cancer, is driven by tumor stimulation of osteoclastic bone resorption. Collective evidence supports the notion that effective therapy for bone metastases should target both the tumor and the bone microenvironment. Indeed, bisphosphonate therapy to block osteoclastic bone resorption, used in conjunction with standard anti-cancer treatments, reduces bone pain, pathologic fracture, and hypercalcemia associated with bone metastases from all tumor types. However, regression and cure of bone metastases have yet to be achieved with the current therapeutic armamentarium. Thus, a better understanding of the molecular mechanisms responsible for this devastating skeletal complication of malignancy is required to develop more effective therapy, with the eventual goal of curing and preventing bone metastases. In the August 15, 2009, issue of Genes & Development, Lu et al. (2009) bring the field closer to this goal. They describe an autocrine/paracrine signaling cascade triggered by metalloproteinases-matrix metalloproteinase-1 (MMP-1) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS1)-and cleavage of epidermal growth factor (EGF) ligands to reduce the ratio of osteoblast-produced receptor activator of NF-kB ligand (RANKL) to osteoprotegerin (OPG) to favor osteoclastogenesis and promote breast cancer osteolysis. These studies, described herein, have important implications for new applications of standard cancer therapy that could result in more effective treatment for bone metastases. Bone metastases: clinical features and current therapyCertain solid tumors-such as breast, prostate, and lung cancer-have a propensity to metastasize to bone to cause bone pain, fracture, hypercalcemia, and paralysis. This morbidity is great: Up to 75% of advanced breast and prostate c...

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Effects of DNA and prostaglandin synthesis inhibitors on the stimulation of bone resorption by epidermal growth factor in fetal rat long-bone cultures.

Cited by 52 publications

References 35 publications

Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures.

Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures.

Epidermal growth factor signalling and bone metastasis

Breaking down bone: new insight into site-specific mechanisms of breast cancer osteolysis mediated by metalloproteinases: Figure 1.

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