Mechanisms of bone metastasis in prostate cancer: clinical implications

Msaouel, Pavlos; Pissimissis, Nikolaos; Halapas, Antonios; Koutsilieris, Michael

doi:10.1016/j.beem.2008.01.011

Cited by 102 publications

(105 citation statements)

References 53 publications

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“…Metastatic tumor cells in the bone dysregulate the coordinated relationship between osteoclastic and osteoblastic functions and promote tumor cell proliferation and bone destruction with the aid of various cytokines and growth factors [8,9]. The pathologic dominance determines the common radiographic patterns of bone lesions that vary from predominantly osteolytic, as commonly seen in breast cancer and multiple myeloma, to predominantly osteoblastic, as commonly seen in prostate cancer [3,4,8,9]. Research studies have demonstrated that the markers of bone resorption are elevated to a greater degree in patients with bone metastases from prostate cancer than bone metastases from any other malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…Despite all the novel diagnostic and therapeutic methods, advanced prostate cancer disease remains incurable, and the median survival between the diagnosis of a clinically evident metastasis in bones and death is approximately 3-5 years [8]. Treatment is mainly palliative and supportive therapy plays an important role in the prevention of skeletal complications and reducing bone pain in these patients.…”

Section: Discussionmentioning

confidence: 99%

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A rare presentation of prostate cancer with diffuse osteolytic metastases and PSA of 7242 ng/ml

Rajendiran¹,

Green²,

Gurdeep³

2011

IJCRI

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Introduction: Bone metastases from prostate cancer are commonly osteoblastic and can result in disabling skeletal complications and affect quality of life. We report a rare case of prostate cancer presenting with diffuse osteolytic metastases. Case Report: A 65-yearold African American man, with no past medical history or specific urologic symptoms, sought medical attention for non-specific pain symptoms. He had metastatic prostate adenocarcinoma, high PSA level (7242 ng/mL) and extensive osteolytic metastases. After one year of therapy with antiandrogens, zoledronic acid and local radiation, patient was asymptomatic and did not suffer disabling skeletal complications. His PSA level has been stable and less than 1 ng/mL. Conclusion: Prostate cancer can rarely present with diffuse osteolytic metastases. Early initiation of supportive treatment, especially the bisphosphonate zoledronic acid, plays a pivotal role in the reduction of disabling skeletal complications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A rare presentation of prostate cancer with diffuse osteolytic metastases and PSA of 7242 ng/ml

Rajendiran¹,

Green²,

Gurdeep³

2011

IJCRI

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“…1 One possible consequence of bone marrow stromal cell (BMSC) paracrine signaling is the induction of PCa cells to undergo neuroendocrine (NE) transdifferentiation. In a previous study, we found that soluble factors produced by two mixed BMSC cell lines, HS5 and HS27a, induced apoptosis and also promoted NE differentiation (NED) of the surviving population in co-cultured osteoblastic LNCaP and C4-2B PCa cell lines, but not in osteolytic PC3 PCa cells.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6

Delk

Farach-Carson

2012

Autophagy

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Keywords: bone metastatic prostate cancer, interleukin-6, paracrine signaling, neuroendocrine differentiation, autophagy Abbreviations: BMSC, bone marrow stromal cell; CM, conditioned media; CQ, chloroquine; IL-6, interleukin-6; LC3, microtubule-associated protein 1 light chain 3; NE, neuroendocrine; NED, neuroendocrine differentiation; PCa, prostate cancer; PE, phosphatidylethanolamine; STAT3, signal transducer and activator of transcription 3Autophagy reallocates nutrients and clears normal cells of damaged proteins and organelles. In the context of metastatic disease, invading cancer cells hijack autophagic processes to survive and adapt in the host microenvironment. We sought to understand how autophagy is regulated in the metastatic niche for prostate cancer (PCa) cells where bone marrow stromal cell (BMSC) paracrine signaling induces PCa neuroendocrine differentiation (NED). In PCa, this transdifferentiation of metastatic PCa cells to neuronal-like cells correlates with advanced disease. Because autophagy provides a survival advantage for cancer cells and promotes cell differentiation, we hypothesized that autophagy mediates PCa NED in the bone. Thus, we determined the ability of paracrine factors in conditioned media (CM) from two separate BMSC subtypes, HS5 and HS27a, to induce autophagy in C4-2 and C4-2B bone metastatic PCa cells by characterizing the autophagy marker, LC3. Unlike HS27a CM, HS5 CM induced LC3 accumulation in PCa cells, suggesting autophagy was induced and indicating that HS5 and HS27a secrete a different milieu of paracrine factors that influence PCa autophagy. We identified interleukin-6 (IL-6), a cytokine more highly expressed in HS5 cells than in HS27a cells, as a paracrine factor that regulates PCa autophagy. Pharmacological inhibition of STAT3 activity did not attenuate LC3 accumulation, implying that IL-6 regulates NED and autophagy through different pathways. Finally, chloroquine inhibition of autophagic flux blocked PCa NED; hence autophagic flux maintains NED. Our studies imply that autophagy is cytoprotective for PCa cells in the bone, thus targeting autophagy is a potential therapeutic strategy.

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“…Breast and prostate cancer together are thought to account for more than 80% of these bone metastases (9). Early detection of bone metastases is important clinically, as the prognosis can change and the treatment regimen can at that point be altered from one of curative therapy to one of palliative treatment (10).…”

Section: Patient Populationmentioning

confidence: 99%

Automated Detection of Sclerotic Metastases in the Thoracolumbar Spine at CT

Burns

Yao²,

Wiese³

et al. 2013

Radiology

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Purpose:To design and validate a computer system for automated detection and quantitative characterization of sclerotic metastases of the thoracolumbar spine on computed tomography (CT) images. Materials and Methods:This retrospective study was approved by the institutional review board and was HIPAA compliant; informed consent was waived. The data set consisted of CT examinations in 49 patients (14 female, 35 male patients; mean age, 57.0 years; range, 12-77 years), demonstrating a total of 532 sclerotic lesions of the spine of greater than 0.3 cm 3 in volume, and in 10 control case patients (four women, six men; mean age, 55.2 years; range, 19-70 years) without spinal lesions. CT examinations were divided into training and test sets, and images were analyzed according to prototypical fully-automated computer-aided detection (CAD) software. Free-response receiver operating characteristic analysis was performed. Results:Lesion detection sensitivity on images in the training set was 90%, relative to reference-standard marked lesions (95% confidence interval [CI]: 83%, 97%), at a false-positive rate (FPR) of 10.8 per patient (95% CI: 6.6, 15.0). For images in the testing set, sensitivity was 79% (95% CI: 74%, 84%), with an FPR of 10.9 per patient (95% CI: 8.5, 13.3). Conclusion:This CAD system successfully identified and segmented sclerotic lesions in the thoracolumbar spine.q RSNA, 2013

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Mechanisms of bone metastasis in prostate cancer: clinical implications

Cited by 102 publications

References 53 publications

A rare presentation of prostate cancer with diffuse osteolytic metastases and PSA of 7242 ng/ml

A rare presentation of prostate cancer with diffuse osteolytic metastases and PSA of 7242 ng/ml

Interleukin-6

Automated Detection of Sclerotic Metastases in the Thoracolumbar Spine at CT

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