Monitoring Metastatic Behavior of Human Tumor Cells in Mice with Species-Specific Polymerase Chain Reaction: Elevated Expression of Angiogenesis and Bone Resorption Stimulators by Breast Cancer in Bone Metastases

Pluijm, Gabri van der; Sijmons, Bianca; Vloedgraven, H. J. M.; Deckers, Martine; Papapoulos, Socrates E.; Löwik, Clemens W.G.M.

doi:10.1359/jbmr.2001.16.6.1077

Cited by 119 publications

(83 citation statements)

References 58 publications

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“…Surgical and analytical procedures were performed while mice were anesthetized. 29,31,32 Intraosseous Inoculation of PC-3M-Pro4/luc ϩ Cells A single cell suspension of PC-3M-Pro4/luc ϩ cells was injected into the right tibiae. 29 -31 The progression of cancer cell growth was monitored weekly by BLI.…”

Section: Animalsmentioning

confidence: 99%

“…3-Amino-9-ethyl-carbazole (Sigma, Buchs, Switzerland) served as chromogen (Sigma). Dissected tissues from animal studies were fixed in 4% paraformaldehyde (pH 6.8), decalcified (only bones) as described previously, and processed for paraffin embedding, sectioning, and staining 32 with PS1 antibodies directed against phosphorylated Smad1.…”

Section: Histomorphometry Histochemistry and Immunohistochemistrymentioning

confidence: 99%

“…This may be particularly true for the bone microenvironment, because bone is a storehouse for TGF␤, and it has been shown that activated TGF␤ is released from bone matrix by bone-resorbing osteoclasts. 29,31,32,42,43 The expression level of E-cadherin appears to be inversely related with prostate cancer grade, and its loss is considered a hallmark of EMT. 23,44,45 Recombinant human BMP7 dose-dependently induced E-cadherin promoter activity (Ͼ150% at 1 g/ml BMP7, P Ͻ 0.01), whereas TGF␤ had no effect (Figure 6a).…”

Section: Bmp7 and Epithelial-to-mesenchymal Transition In Prostate Camentioning

confidence: 99%

“…*P Յ 0.01 versus Co (a); *P Ͻ 0.05 versus Co, **P Ͻ 0. bone marrow. 31,32,42,43 Compelling evidence suggests that the formation of micrometastatic deposits in bone marrow and subsequent development into clinically overt (macro)metastasis are critically dependent on the tumorbone (marrow) interactions, in particular bone remodeling. 31,43,52 Although little is known regarding the impact of bone (marrow) stromal cells in prostate cancer bone metastasis, it can be argued that the production and release of specific growth factors, colony stimulating factors, and cytokines like Wnts, which are critically important for the maintenance of the hematopoietic stem cell niche (and which regulate hematopoiesis), may also be essential for colonization, survival, and growth of cancer cells.…”

Section: Bmp7 and Prostatementioning

confidence: 99%

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BMP7, a Putative Regulator of Epithelial Homeostasis in the Human Prostate, Is a Potent Inhibitor of Prostate Cancer Bone Metastasis in Vivo

Buijs

Rentsch

Horst

et al. 2007

The American Journal of Pathology

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182

161

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Bone morphogenic protein 7 (BMP7) counteracts physiological epithelial-to-mesenchymal transition, a process that is indicative of epithelial plasticity. Because epithelial-to-mesenchymal transition is involved in cancer, we investigated whether BMP7 plays a role in prostate cancer growth and metastasis. BMP7 expression in laser-microdissected primary human prostate cancer tissue was strongly down-regulated compared with normal prostate luminal epithelium. Furthermore, BMP7 expression in prostate cancer cell lines was inversely related to tumorigenic and metastatic potential in vivo and significantly correlated to E-cadherin/vimentin ratios. Exogenous addition of BMP7 to human prostate cancer cells dose-dependently inhibited transforming growth factor ␤-induced activation of nuclear Smad3/4 complexes via ALK5 and induced E-cadherin expression. Moreover, BMP7-induced activation of nuclear Smad1/4/5 signaling transduced via BMP type I receptors was synergistically stimulated in the presence of transforming growth factor ␤, a growth factor that is enriched in the bone microenvironment. Daily BMP7 administration to nude mice inhibited the growth of cancer cells in bone. In contrast, no significant growth inhibitory effect of BMP7 was observed in intraprostatic xenografts. Collectively, our observations suggest that BMP7 controls and preserves the epithelial phenotype

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Section: Animalsmentioning

confidence: 99%

Section: Histomorphometry Histochemistry and Immunohistochemistrymentioning

confidence: 99%

Section: Bmp7 and Epithelial-to-mesenchymal Transition In Prostate Camentioning

confidence: 99%

Section: Bmp7 and Prostatementioning

confidence: 99%

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BMP7, a Putative Regulator of Epithelial Homeostasis in the Human Prostate, Is a Potent Inhibitor of Prostate Cancer Bone Metastasis in Vivo

Buijs

Rentsch

Horst

et al. 2007

The American Journal of Pathology

Self Cite

182

161

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“…The environment is further enriched as the tumour cells stimulate osteoclastic bone resorption, leading to the release of more bone-derived growth factors that enhance survival and growth of the cancer, while simultaneously disrupting normal bone remodelling thus resulting in bone destruction. van der Pluijm et al (2001) elegantly demonstrated that several mRNAs are increased in bone versus non-bone sites of human breast cancer metastases in nude mice. RNA abundances were determined by species-specific RT-PCR.…”

Section: Osteolytic Metastasesmentioning

confidence: 99%

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

Clines

Guise²

2005

Endocr Relat Cancer

229

211

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Calcium homeostasis is a tightly regulated process involving the co-ordinated efforts of the skeleton, kidney, parathyroid glands and intestine. Neoplasms can alter this homeostasis indirectly through the production of endocrine factors resulting in humoral hypercalcaemia of malignancy. Relatively common with breast and lung cancer, this paraneoplastic condition is most often due to tumour production of parathyroid hormone-related protein and ensuing increased osteoclastic bone resorption. Although control of hypercalcaemia is generally successful, the development of this complication is associated with a poor prognosis. The metastasis of tumour cells to bone represents another skeletal complication of malignancy. As explained in the 'seed and soil' hypothesis, bone represents a fertile ground for cancer cells to flourish. The molecular mechanisms of this mutually beneficial relationship between bone and cancer cells are beginning to be understood. In the case of osteolytic bone disease, tumour-produced parathyroid hormone-related protein stimulates osteoclasts that in turn secrete tumour-activating transforming growth factor-b that further stimulates local cancer cells. This 'vicious cycle' of bone metastases represents reciprocal bone/ cancer cellular signals that likely modulate osteoblastic bone metastatic lesions as well. The development of targeted therapies to either block initial cancer cell chemotaxis, invasion and adhesion or to break the 'vicious cycle' is dependent on a more complete understanding of bone metastases. Although bisphosphonates delay progression of skeletal metastases, it is clear that more effective therapies are needed. Cancer-associated bone morbidity remains a major public health problem, and to improve therapy and prevention it is important to understand the pathophysiology of the effects of cancer on bone. This review will detail scientific advances regarding this area.

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Nonspherical femoral head shape (pistol grip deformity), neck shaft angle, and risk of hip osteoarthritis: A case–control study

Doherty¹,

Courtney²,

Doherty³

et al. 2008

Arthritis & Rheumatism

191

148

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Objective. To determine whether 2-dimensional measures of femoral head shape and angle are associated with hip osteoarthritis (OA).Methods. We compared cases with symptomatic radiographic hip OA with asymptomatic controls with no radiographic hip OA. On anteroposterior pelvis radiographs, we measured "pistol grip deformity" for each hip (visually categorized as nonspherical, indeterminate, or spherical), the femoral head-to-femoral neck ratio as an interval measure of femoral head shape, and the femoral neck shaft angle. The relative risk of hip OA associated with each feature was estimated using odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for possible confounders using a logistic regression model. Conclusion.Our findings indicate that pistol grip deformity is associated with hip OA. The increased prevalence of pistol grip deformity and an abnormally low neck shaft angle in unaffected hips of cases with unilateral OA suggests that they are risk factors for development of hip OA. However, both a nonspherical head shape and an increase in neck shaft angle may occur as a consequence of OA.Osteoarthritis (OA) of the hip is an important cause of pain and disability in the community (1,2). As with OA at other sites, hip OA is considered a common complex disorder with multiple genetic, constitutional, and environmental risk factors that result in heterogeneity of phenotype and variability in clinical outcome (3,4). Hip OA shows marked familial predisposition, with heritability estimates of 0.6 in women (5) and up to a 5-fold increased risk in siblings of patients undergoing

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Monitoring Metastatic Behavior of Human Tumor Cells in Mice with Species-Specific Polymerase Chain Reaction: Elevated Expression of Angiogenesis and Bone Resorption Stimulators by Breast Cancer in Bone Metastases

Cited by 119 publications

References 58 publications

BMP7, a Putative Regulator of Epithelial Homeostasis in the Human Prostate, Is a Potent Inhibitor of Prostate Cancer Bone Metastasis in Vivo

BMP7, a Putative Regulator of Epithelial Homeostasis in the Human Prostate, Is a Potent Inhibitor of Prostate Cancer Bone Metastasis in Vivo

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

Nonspherical femoral head shape (pistol grip deformity), neck shaft angle, and risk of hip osteoarthritis: A case–control study

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