Intraosseous growth of human prostate cancer in implanted adult human bone: Relationship of prostate cancer cells to osteoclasts in osteoblastic metastatic lesions

Yonou, Hiroyuki; Ochiai, Atsushi; Goya, Masato; Kanomata, Naoki; Hokama, Seitetsu; Morozumi, Makoto; Sugaya, Kimio; Hatano, Tadashi; Ogawa, Yoshihide

doi:10.1002/pros.10349

Cited by 43 publications

(27 citation statements)

References 25 publications

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“…The most investigated classes of bone-targeted agents that have an inhibitory effect on osteolysis are the bisphosphonates and the monoclonal antibody against RANKL, denosumab [42]. Even in osteoblastic bone metastases from prostate cancer, there is an increased bone resorption phase providing the rationale for treatment with osteoclast-targeted agents [47,48].…”

Section: Metastasis To Bonementioning

confidence: 99%

Metastatic Tumors to the Jaws and Mouth

Hirshberg

Berger

Allon

et al. 2014

Head and Neck Pathol

156

171

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Metastatic dissemination to the oral cavity is rare and is usually the evidence of a wide spread disease with an average survival rate of 7 months. In almost a quarter of the cases, oral metastasis was found to be the first indication of an occult malignancy at a distant site. Metastatic lesions can be found anywhere in the oral cavity, however, the jawbones with the molar area is the most frequently involved site. In the oral soft tissues, the gingiva is the most common site, suggesting the possible role of inflammation in the attraction of metastatic deposits. The most common primary malignancies presenting oral metastases were the lung, kidney, liver, and prostate for men, and breast, female genital organs, kidney, and colorectum for women. Most patients with jawbone metastasis complain of swelling, pain, and paresthesia. An exophytic lesion is the most common clinical presentation of metastatic lesions in the oral soft tissues. Early lesions, mainly those located in the gingiva, may resemble a hyperplastic or reactive lesion. Once a lesion is recognized as metastasis, the primary tumor site should be identified following clinical, radiological and histopathological investigations. If standardized diagnostic workup fails to detect the site of origin, then the term carcinoma of unknown primary is applied. Personalized medicine tools such as tissue-oforigin assays should be applied, either by immunohistochemical testing or by molecular-profiling methods as these may lead to a more favorable outcome.

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Section: Metastasis To Bonementioning

confidence: 99%

Metastatic Tumors to the Jaws and Mouth

Hirshberg

Berger

Allon

et al. 2014

Head and Neck Pathol

156

171

View full text Add to dashboard Cite

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“…There is evidence that osteoblastic metastasis also involves considerable osteolysis [46,47]. In prostate cancer patients with clinical osteoblastic lesions, blood and urinary levels of bone resorption markers are often elevated [48].…”

Section: Osteoblastic Bone Metastasismentioning

confidence: 99%

“…Clinical trials have suggested that blocking osteoclastic bone resorption reduces related skeletal events in prostate cancer patients [49]. In a mouse model of bone metastasis, osteoclasts numbers were shown to markedly increase at sites of early tumor invasion [47]. One theory as to why osteoclastogenessis is important for osteoblastic bone metastasis is that bone resorption by osteoclasts releases a variety of growth factors, which are stored as inactive forms in the bone matrix.…”

Section: Osteoblastic Bone Metastasismentioning

confidence: 99%

Mechanisms of cancer metastasis to the bone

Yin¹,

Pollock²,

Kelly³

2005

Cell Res

298

226

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Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. What is the basis for their preferential growth within the bone microenvironment? Bidirectional interactions between tumor cells and cells that make up bone result in a selective advantage for tumor growth and can lead to bone destruction or new bone matrix deposition. This review discusses our current understanding of the molecular components and mechanisms that are responsible for those interactions.

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“…that result from bone metastases and multiple myeloma. Osteoclast involvement is observed in all types of cancer-induced bone destruction, regardless of the lesions' radiographic appearance as either osteolytic or osteoblastic, and irrespective of the tumor type of origin (5)(6)(7).…”

Section: Control Of Normal Bone Remodeling By the Rank/rankl Pathwaymentioning

confidence: 97%

Molecular Pathways: Osteoclast-Dependent and Osteoclast-Independent Roles of the RANKL/RANK/OPG Pathway in Tumorigenesis and Metastasis

Dougall

2012

Clinical Cancer Research

175

162

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Receptor activator of nuclear factor-kappa B ligand (RANKL) is a TNF ligand superfamily member that is essential for the formation, activation, and function of osteoclasts. RANKL functions via its cognate receptor RANK, and it is inhibited by the soluble decoy receptor osteoprotegerin (OPG). In skeletal metastases, the ratio of RANKL to OPG is upregulated, which leads to increased osteoclast-mediated bone destruction. These changes in the bone microenvironment not only compromise the structural integrity of bone, leading to severe clinical morbidities, but have also been implicated in establishment of de novo bone metastasis and the progression of existing skeletal tumors. Evaluation of RANKL inhibitors, including the fully human anti-RANKL antibody denosumab, in patients with cancer has shown reductions in tumor-induced bone resorption activity and successful management of skeletal complications of bone metastases. RANKL also functions as a major paracrine effector of the mitogenic action of progesterone in mouse mammary epithelium, and it has a role in ovarian hormone-dependent expansion and regenerative potential of mammary stem cells. RANKL inhibition attenuates mammary tumorigenesis and pulmonary metastases in mouse models. These data suggest that the contribution of progesterone to increased mammary cancer incidence is mediated, at least in part, by RANKL-dependent changes in the mammary epithelium; RANKL also directly promotes distant metastases. In summary, the antitumor and antimetastatic effects of RANKL inhibition can occur by at least 2 distinct mechanisms, one in the bone via osteoclast-dependent effects, and the second via direct effects on the tumor cells of various origins and/or mammary epithelium. Clin Cancer Res; 18(2); 326-35. Ó2011 AACR.

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Intraosseous growth of human prostate cancer in implanted adult human bone: Relationship of prostate cancer cells to osteoclasts in osteoblastic metastatic lesions

Abstract: The predominance of osteoblastic change with resorption may lead to bone remodeling in metastatic lesions, and osteoclasts may play an important role in bone metastasis from prostate cancer.

Cited by 43 publications

References 25 publications

Metastatic Tumors to the Jaws and Mouth

Metastatic Tumors to the Jaws and Mouth

Mechanisms of cancer metastasis to the bone

Molecular Pathways: Osteoclast-Dependent and Osteoclast-Independent Roles of the RANKL/RANK/OPG Pathway in Tumorigenesis and Metastasis

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