Stromal and epithelial cells of the canine prostate express parathyroid hormone-related protein, but not the PTH/PTHrP receptor

Blomme, Eric A.G.; Sugimoto, Yasuro; McCauley, Laurie K.; Lin, Yi‐Chia; Capen, Charles C.; Rosol, Thomas J.

doi:10.1002/(sici)1097-0045(19980701)36:2<110::aid-pros6>3.0.co;2-m

Cited by 15 publications

(4 citation statements)

References 51 publications

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“…The role of the PTHrP receptor has not previously been described clearly in benign or malignant human prostate tissue. Immuno-histochemistry has failed to demonstrate the PTHrP receptor in the canine model of benign prostate (Blomme et al, 1998), which would be consistent with the lack of growth factor response to PTHrP found in benign prostate by Peehl et al (1997).…”

Section: Clinicalsupporting

confidence: 82%

Parathyroid hormone related peptide and receptor expression in paired primary prostate cancer and bone metastases

et al. 2002

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Parathyroid hormone-related peptide is a regulatory protein implicated in the pathogenesis of bone metastases, particularly in breast carcinoma. Parathyroid hormone-related peptide is widely expressed in primary prostate cancers but there are few reports of its expression in prostatic metastases. The aim of this study was to examine the expression of parathyroid hormonerelated peptide and its receptor in matched primary and in bone metastatic tissue from patients with untreated adenocarcinoma of the prostate. Eight-millimetre trephine iliac crest bone biopsies containing metastatic prostate cancer were obtained from 14 patients from whom matched primary tumour tissue was also available. Histological grading was performed by an independent pathologist. The cellular location of mRNA for parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor was identified using in situ hybridization with 35 S-labelled probe. Expression of parathyroid hormone-related peptide and its receptor was described as uniform, heterogenous or negative within the tumour cell population. Parathyroid hormonerelated peptide expression was positive in 13 out of 14 primary tumours and in all 14 metastases. Receptor expression was evident in all 14 primaries and 12 out of 14 metastases. Co-expression of parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor was common (13 primary tumours, 12 metastases). The co-expression of parathyroid hormone-related peptide and its receptor suggest that autocrine parathyroid hormone-related peptide mediated stimulation may be a mechanism of escape from normal growth regulatory pathways. The high frequency of parathyroid hormone-related peptide expression in metastases is consistent with a role in the pathogenesis of bone metastases.

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Section: Clinicalsupporting

confidence: 82%

Parathyroid hormone related peptide and receptor expression in paired primary prostate cancer and bone metastases

et al. 2002

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“…The growing prostate cancer cells secrete PSA and PTH-rp [135][136][137], and deposit a matrix protein, thrombospondin-1 (unpublished results). PSA will degrade PTH-rp and limit its biologic activity [140,141].…”

Section: Intermediate Phase Of Bone Metastasismentioning

confidence: 88%

Osteomimetic properties of prostate cancer cells: A hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment

1999

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BACKGROUND Unlike most other malignancies, prostate cancer metastasizes preferentially to the skeleton and elicits osteoblastic reactions. METHODS We present a hypothesis, based upon results obtained from our laboratory and others, on the nature of progression of prostate cancer cells and their predilection to growth and metastasis in the bone microenvironment. We propose the hypothesis that osseous metastatic prostate cancer cells must be osteomimetic in order to metastasize, grow, and survive in the skeleton. The reciprocal interaction between prostate cancer and bone stromal growth factors, including basic fibroblast growth factor (bFGF), hepatocyte growth factor/scatter factor (HGF/SF), and especially the insulin growth factor (IGF) axis initiates bone tropism, and is enhanced by prostate secreted endothelin‐1 (ET‐1) and urokinase‐type plasminogen activator (uPA). Growth factors and peptides that have differentiating activity, such as transforming growth factor beta (TGF‐β), parathyroid hormone‐related protein (PTH‐rp), and the bone morphogenetic proteins (BMPs), can shift local homeostasis to produce the characteristic blastic phenotype, via interaction with prostate‐secreted human kalikrein 2 (hK2), and prostate‐specific antigen (PSA). This proposal asserts that altering the expression of certain critical transcription factors, such as Cbfa and MSX in prostate cancer cells, which presumably are under the inductive influences of prostate or bone stromal cells, can confer profiles of gene expression, such as osteopontin (OPN), osteocalcin (OC), and bone sialoprotein (BSP), that mimic that of osteoblasts. RESULTS AND CONCLUSIONS Elucidation of common proteins, presumably driven by the same promoters, expressed by both prostate cancer and bone stromal cells, could result in the development of novel preventive and therapeutic strategies for the treatment of prostate cancer skeletal metastasis. Agents developed using these strategies could have the potential advantage of interfering with growth and enhancing apoptosis in both prostate cancer and bone stromal compartments. The selective application of gene therapy strategy, driven by tissue‐specific and tumor‐restricted promoters for the safe delivery and expression of therapeutic genes in experimental models of prostate cancer metastasis, is discussed. Prostate 39:246–261, 1999. © 1999 Wiley‐Liss, Inc.

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“…Another benefit is the use of prostatic tissue rather than a cell line, which may more closely represent the complex microenvironment of metastases. Canine prostate, in particular, is uniquely useful since it is known to produce bioactive factors (such as endothelin and parathyroid hormone-related peptide) that are also produced in the human prostate and are thought to be important in the pathogenesis of osteoblastic metastases [40,41].…”

Section: Dogs In Prostate Cancer Researchmentioning

confidence: 99%

Review of Animal Models of Prostate Cancer Bone Metastasis

Simmons

Elshafae

Keller

et al. 2014

Veterinary Sciences

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Prostate cancer bone metastases are associated with a poor prognosis and are considered incurable. Insight into the formation and growth of prostate cancer bone metastasis is required for development of new imaging and therapeutic strategies to combat this devastating disease. Animal models are indispensable in investigating cancer pathogenesis and evaluating therapeutics. Multiple animal models of prostate cancer bone metastasis have been developed, but few effectively model prostatic neoplasms and osteoblastic bone metastases as they occur in men. This review discusses the animal models that have been developed to investigate prostate cancer bone metastasis, with a focus on canine models and also includes human xenograft and rodent models. Adult dogs spontaneously develop benign prostatic hyperplasia and prostate cancer with osteoblastic bone metastases. Large animal models, such as dogs, are needed to develop new molecular imaging tools and effective focal intraprostatic therapy. None of the available models fully reflect the metastatic disease seen in men, although the various models have provided important insight into the metastatic process. As additional models are developed and knowledge from the different models is combined, the molecular mechanisms of prostate cancer bone metastasis can be deciphered and targeted for development of novel therapies and molecular diagnostic imaging.

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Stromal and epithelial cells of the canine prostate express parathyroid hormone-related protein, but not the PTH/PTHrP receptor

Cited by 15 publications

References 51 publications

Parathyroid hormone related peptide and receptor expression in paired primary prostate cancer and bone metastases

Parathyroid hormone related peptide and receptor expression in paired primary prostate cancer and bone metastases

Osteomimetic properties of prostate cancer cells: A hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment

Review of Animal Models of Prostate Cancer Bone Metastasis

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