Total and regional bone mass and biochemical markers of bone remodeling in metastatic prostate cancer

Revilla, M.; Arribas, Ignacio; Sánchez‐Chapado, Manuel; Villa, L.F.; Bethencourt, Fermín Rodríguez de; Rico, H.

doi:10.1002/(sici)1097-0045(19980601)35:4<243::aid-pros2>3.0.co;2-h

Cited by 20 publications

(5 citation statements)

References 26 publications

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“…Although these studies have provided insight into the mechanisms that generate and maintain bone cancer pain, the tumor cells that were employed were primarily osteolytic or bonedestroying in nature (34)(35)(36). A major question is whether these studies will accurately predict the mechanisms that generate the bone pain driven by tumor cells, such as prostate, that are primarily bone-forming rather than bone-destroying resulting from an upset in the balance between osteoblastic or osteolytic activity in the tumor-bearing femur (37). For this reason, we focused on the ACE-1 canine prostate tumor cells, as when these cells are implanted into the femur of nude mice, significant new ''woven'' bone is formed in local compartments, giving the bone a unique scalloped appearance similar to what is observed in humans with prostate tumor metastases to bone (6).…”

Section: Discussionmentioning

confidence: 99%

A Blocking Antibody to Nerve Growth Factor Attenuates Skeletal Pain Induced by Prostate Tumor Cells Growing in Bone

et al. 2005

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Prostate cancer is unique in that bone is often the only clinically detectable site of metastasis. Prostate tumors that have metastasized to bone frequently induce bone pain which can be difficult to fully control as it seems to be driven simultaneously by inflammatory, neuropathic, and tumorigenic mechanisms. As nerve growth factor (NGF) has been shown to modulate inflammatory and some neuropathic pain states in animal models, an NGF-sequestering antibody was administered in a prostate model of bone cancer where significant bone formation and bone destruction occur simultaneously in the mouse femur. Administration of a blocking antibody to NGF produced a significant reduction in both early and late stage bone cancer pain-related behaviors that was greater than or equivalent to that achieved with acute administration of 10 or 30 mg/kg of morphine sulfate. In contrast, this therapy did not influence tumor-induced bone remodeling, osteoblast proliferation, osteoclastogenesis, tumor growth, or markers of sensory or sympathetic innervation in the skin or bone. One rather unique aspect of the sensory innervation of bone, that may partially explain the analgesic efficacy of anti-NGF therapy in relieving prostate cancer-induced bone pain, is that nearly all nerve fibers that innervate the bone express trkA and p75, and these are the receptors through which NGF sensitizes and/or activates nociceptors. The present results suggest that anti-NGF therapy may be effective in reducing pain and enhancing the quality of life in patients with prostate tumor-induced bone cancer pain. (Cancer Res 2005; 65(20): 9426-35)

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Section: Discussionmentioning

confidence: 99%

A Blocking Antibody to Nerve Growth Factor Attenuates Skeletal Pain Induced by Prostate Tumor Cells Growing in Bone

et al. 2005

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“…Metastatic prostate cancer cells alter the normal bone remodeling balance involving interactions between osteoblasts, osteoclasts, and constituents of the bone matrix to favor bone formation. Both osteoblastic and osteolytic changes occur during the course of tumor progression as a consequence of significant bone resorption and bone production occurring within the metastatic sites (51,52). Although some components of bone remodeling involving tumor metastases have been identified, including PTHrP and transforming growth factor ␤ (52), the process remains ill-defined.…”

Section: Discussionmentioning

confidence: 99%

Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression

Nelson

Gan

Ferguson

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

196

159

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The identification of genes with selective expression in specific organs or cell types provides an entry point for understanding biological processes that occur uniquely within a particular tissue. Using a subtraction approach designed to identify genes preferentially expressed in specific tissues, we have identified prostase, a human serine protease with prostate-restricted expression. The prostase cDNA encodes a putative 254-aa polypeptide with a conserved serine protease catalytic triad and an amino-terminal pre-propeptide sequence, indicating a potential secretory function. The genomic sequence comprises five exons and four introns and contains multiple copies of a chromosome 19q-specific minisatellite repeat. Northern analysis indicates that prostase mRNA is expressed in hormonally responsive normal and neoplastic prostate epithelial tissues, but not in prostate stromal constituents. Prostase shares 35% amino acid identity with prostate-specific antigen (PSA) and 78% identity with the porcine enamel matrix serine proteinase 1, an enzyme involved in enamel matrix degradation and with a putative role in the disruption of intercellular junctions. Radiation-hybrid-panel mapping localized prostase to chromosome 19q13, a region containing several other serine proteases, including protease M, pancreatic͞renal kallikrein hK1, and the prostate-specific kallikreins hK2 and hK3 (PSA). The sequence homology between prostase and other well-characterized serine proteases suggests several potential functional roles for the prostase protein that include the degradation of extracellular matrix and the activation of PSA and other proteases.

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“…In a study involving 83 specimens from 70 patients with prostatic cancer (32 with and 38 without bone metastasis), the pyridinoline cross-linked carboxyterminal telopeptide (CTP) level was correlated with the extent of disease score more than PSA and other bone markers [64]. In another study, the level of TRAP (a bone resorption marker) and total regional bone mineral content (BMC) measured in 64 patients (32 patients and 32 controls) was found to be significantly different in the pelvis, legs, and trunk of patients compared to the control [66]. These findings confirmed a corresponding increase in bone resorptive (osteoclastic) activity alongside bone osteoblastic activity during bone metastasis [64,65].…”

Section: The Underlying Molecular Mechanisms In Prostate Cancer Bomentioning

confidence: 99%

Prostate Cancer and Bone Metastases: The Underlying Mechanisms

Wong

Mohamad

Giaze

et al. 2019

IJMS

129

102

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Patients with advanced prostate cancer often develop bone metastases, leading to bone pain, skeletal fracture, and increased mortality. Bone provides a hospitable microenvironment to tumor cells. The disease manifestation is driven by the interaction between invading tumor cells, bone-forming osteoblasts, and bone-resorbing osteoclasts. The increased level of osteoclast-activating factor (parathyroid hormone-related peptide, PTHrP) is believed to induce bone resorption by upregulating receptor activator of nuclear factor-kappa B ligand (RANKL) and the release of various growth factors into the bone microenvironment to enhance cancer cell growth. However, the underlying molecular mechanisms remain poorly understood. This review outlines the possible molecular mechanisms involved in governing bone metastases driven by prostate cancer, which further provide the basis in searching for new molecular targets for the development of potential therapy.

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Total and regional bone mass and biochemical markers of bone remodeling in metastatic prostate cancer

Cited by 20 publications

References 26 publications

A Blocking Antibody to Nerve Growth Factor Attenuates Skeletal Pain Induced by Prostate Tumor Cells Growing in Bone

A Blocking Antibody to Nerve Growth Factor Attenuates Skeletal Pain Induced by Prostate Tumor Cells Growing in Bone

Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression

Prostate Cancer and Bone Metastases: The Underlying Mechanisms

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