Histomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer

Taube, T.; Elomaa, Inkeri; Blomqvist, Carl; Benéton, M. N. C.; Kanis, John А.

doi:10.1016/8756-3282(94)90703-x

Cited by 167 publications

(101 citation statements)

References 26 publications

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“…In vivo, however, it appears that tumour cells are not active effectors of bone destruction, particularly during the establishment of metastasis. Histological analysis and scanning electron microscopy of osteolytic bone metastases indicate that osteoclasts adjacent to tumour cells actively resorb bone (Boyde et al 1986, Taube et al 1994). This would suggest that breast cancer cells have the ability to stimulate osteoclastic bone resorption.…”

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

230

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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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

230

211

View full text Add to dashboard Cite

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“…The bone extracellular matrix is rich in growth factors (Hauschka et al, 1986), which are released during the continuous remodelling process and favour cancer cell proliferation and survival (Barnes, 1988;Geier et al, 1992;Quinn et al, 1996). On the other hand, breast cancer cells are able to stimulate bone resorption by increasing osteoclast recruitment and proliferation as well as the activity of mature osteoclasts (Mundy, 1991;Taube et al, 1994;Yoneda et al, 2000). Bone microenvironment will then be even more enriched in bone-derived growth factors that enhance proliferation and survival of cancer cells.…”

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confidence: 99%

Bisphosphonates antagonise bone growth factors' effects on human breast cancer cells survival

2003

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Bone tissue constitutes a fertile 'soil' for metastatic tumours, notably breast cancer. High concentrations of growth factors in bone matrix favour cancer cell proliferation and survival, and a vicious cycle settles between bone matrix, osteoclasts and cancer cells. Classically, bisphosphonates interrupt this vicious cycle by inhibiting osteoclast-mediated bone resorption. We and others recently reported that bisphosphonates can also induce human breast cancer cell death in vitro, which could contribute to their beneficial clinical effects. We hypothesised that bisphosphonates could inhibit the favourable effects of 'bone -derived' growth factors, and indeed found that bisphosphonates reduced or abolished the stimulatory effects of growth factors (IGFs, FGF-2) on MCF-7 and T47D cell proliferation and inhibited their protective effects on apoptotic cell death in vitro under serum-free conditions. This could happen through an interaction with growth factors' intracellular phosphorylation transduction pathways, such as ERK1/2-MAPK. In conclusion, we report that bisphosphonates antagonised the stimulatory effects of growth factors on human breast cancer cell survival and reduced their protective effects against apoptotic cell death. Bisphosphonates and growth factors thus appear to be concurrent compounds for tumour cell growth and survival in bone tissue. This could represent a new mechanism of action of bisphosphonates in their protective effects against breast cancer-induced osteolysis.

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“…In addition to focal skeletal disease, there is evidence that breast cancer is associated with generalized disturbances in skeletal metabolism.Increased resorption and accelerated turnover of bone have been shown in biopsies taken at sites distant from skeletal metastases (Taube et al, 1994), perhaps mediated by the systemic secretion of parathyroid hormone-related protein (PTHrP) which is expressed in breast cancer tissue (Orloff et al, 1989;Powell et al, 1991).In addition to the expression of PTHrP, both chemotherapy and a chemotherapy-induced menopause are likely to increase the risk of osteoporosis (Rivkees and Crawford, 1988;Saarto et al, 1997). Whereas tamoxifen may protect against bone loss in postmenopausal women, recent evidence suggests that bone losses may be accelerated in women with normal ovarian function Saarto et al, 1997).…”

mentioning

confidence: 99%

“…Increased resorption and accelerated turnover of bone have been shown in biopsies taken at sites distant from skeletal metastases (Taube et al, 1994), perhaps mediated by the systemic secretion of parathyroid hormone-related protein (PTHrP) which is expressed in breast cancer tissue (Orloff et al, 1989;Powell et al, 1991).…”

mentioning

confidence: 99%

A high incidence of vertebral fracture in women with breast cancer

et al. 1999

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Metastases from breast cancer appear to have a predilection for the skeleton. In addition to focal skeletal disease, there is evidence that breast cancer is associated with generalized disturbances in skeletal metabolism.Increased resorption and accelerated turnover of bone have been shown in biopsies taken at sites distant from skeletal metastases (Taube et al, 1994), perhaps mediated by the systemic secretion of parathyroid hormone-related protein (PTHrP) which is expressed in breast cancer tissue (Orloff et al, 1989;Powell et al, 1991).In addition to the expression of PTHrP, both chemotherapy and a chemotherapy-induced menopause are likely to increase the risk of osteoporosis (Rivkees and Crawford, 1988;Saarto et al, 1997). Whereas tamoxifen may protect against bone loss in postmenopausal women, recent evidence suggests that bone losses may be accelerated in women with normal ovarian function Saarto et al, 1997). For these reasons, we wished to determine whether the risk of osteoporotic fractures was higher in women with non-metastatic breast cancer than in the healthy population. PATIENTS AND METHODSWe studied two populations of women with breast cancer and a control population of women randomly drawn from the female population. Eighty-two women had histologically proven breast cancer and recurrent disease diagnosed according to standard criteria (Breast Cancer Task Force, 1977;Hayward et al, 1978), but without skeletal metastases as judged by skeletal radiographs and scintigraphy. They comprised a cohort of women in whom the effects of clodronate on the incidence of skeletal metastases and associated morbidity were studied. The findings of this trial have been published elsewhere .After initial assessment, patients were randomized to receive clodronate by mouth, 1600 mg daily as four capsules, or an identical placebo supplied by Leiras Oy, Helsinki, Finland. Patients were instructed to take four capsules daily in the morning 1 h before meals and away from calcium-containing liquids. Bone scintigraphy and skeletal radiographs (hands, pelvis, skull, lateral lumbar and thoracic spine) were obtained at 6-monthly intervals.The second population of women with breast cancer comprised 352 women recruited at the time of the first diagnosis to study the effects of clodronate, 1600 mg daily by mouth, on the incidence of skeletal metastases. None of the women had radiographic or scintigraphic evidence of skeletal disease. No selection was made on the basis of histological grade or the involvement of axillary nodes. After diagnosis, 36% of women received tamoxifen, 18% chemotherapy and 43% both chemotherapy and tamoxifen. After randomization to clodronate or placebo treatment, patients were assessed at 6-monthly intervals and spinal radiographs taken yearly. The study is continuing and remains double blind, so that the data are presented irrespective of treatment allocation.A control population comprised 776 women aged 45Ð69 years randomly drawn from a catchment population in London . At initial assessment, 193 women (2...

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Histomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer

Cited by 167 publications

References 26 publications

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

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

Bisphosphonates antagonise bone growth factors' effects on human breast cancer cells survival

A high incidence of vertebral fracture in women with breast cancer

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