Review of Animal Models of Prostate Cancer Bone Metastasis

Simmons, Jessica K.; Elshafae, Said M.; Keller, Evan T.; McCauley, Laurie K.; Rosol, Thomas J.

doi:10.3390/vetsci1010016

Cited by 20 publications

(19 citation statements)

References 98 publications

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“…In this study, we used a well described model of canine prostate cancer (Ace-1) that mimics prostate cancer in men (including mixed osteoblastic/osteolytic bone metastases) to investigate the role of the human GRPr on prostate cancer growth and progression [21]. Ace-1 cells are tumorigenic in immunocompromised mice and rats and develop mixed osteoblastic/osteolytic bone metastases after intracardiac injection into the left ventricle [30]. The Ace-1 cells are a valuable model of bone metastasis, including studies on pain associated with bone metastases [31,32].…”

Section: Discussionmentioning

confidence: 99%

Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer

et al. 2016

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BACKGROUND The gastrin-releasing peptide receptor (GRPr) is upregulated in early and late-stage human prostate cancer (PCa) and other solid tumors of the mammary gland, lung, head and neck, colon, uterus, ovary, and kidney. However, little is known about its role in prostate cancer. This study examined the effects of a heterologous GRPr agonist, bombesin (BBN), on growth, motility, morphology, gene expression, and tumor phenotype of an osteoblastic canine prostate cancer cell line (Ace-1) in vitro and in vivo. METHODS The Ace-1 cells were stably transfected with the human GRPr and tumor cells were grown in vitro and as subcutaneous and intratibial tumors in nude mice. The effect of BBN was measured on cell proliferation, cell migration, tumor growth (using bioluminescence), tumor cell morphology, bone tumor phenotype, and epithelial-mesenchymal transition (EMT) and metastasis gene expression (quantitative RT-PCR). GRPr mRNA expression was measured in primary canine prostate cancers and normal prostate glands. RESULTS Bombesin (BBN) increased tumor cell proliferation and migration in vitro and tumor growth and invasion in vivo. BBN upregulated epithelial-to-mesenchymal transition (EMT) markers (TWIST, SNAIL, and SLUG mRNA) and downregulated epithelial markers (E-cadherin and β-catenin mRNA), and modified tumor cell morphology to a spindle cell phenotype. Blockade of GRPr upregulated E-cadherin and downregulated VIMENTIN and SNAIL mRNA. BBN altered the in vivo tumor phenotype in bone from an osteoblastic to osteolytic phenotype. Primary canine prostate cancers had increased GRPr mRNA expression compared to normal prostates. CONCLUSION These data demonstrated that the GRPr is important in prostate cancer growth and progression and targeting GRPr may be a promising strategy for treatment of prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer

et al. 2016

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“…Animal models of prostate cancer have recently been extensively reviewed, and prostate cancer bone metastasis research will be highlighted in this review. 123 …”

Section: Animal Modelsmentioning

confidence: 99%

Animal Models of Bone Metastasis

et al. 2015

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Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone.

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“…Although most human prostate cancer patients respond to androgen deprivation therapy initially, men with metastatic prostate cancer often develop aggressive androgen‐independent prostate cancer (AIPC) after therapy 67 . AR signaling remains active in most AIPC patients, which is in contrast to dogs with advanced PCa 68,69 . Despite this difference, canine PCa shares similar characteristics (clinical presentation, pathogenesis, and bone metastasis phenotype) with advanced human androgen refractory prostate cancer making the dog cancer cell lines valuable models for studying androgen‐independent PCa 69,70 …”

Section: Discussionmentioning

confidence: 99%

“…AR signaling remains active in most AIPC patients, which is in contrast to dogs with advanced PCa 68,69 . Despite this difference, canine PCa shares similar characteristics (clinical presentation, pathogenesis, and bone metastasis phenotype) with advanced human androgen refractory prostate cancer making the dog cancer cell lines valuable models for studying androgen‐independent PCa 69,70 …”

Section: Discussionmentioning

confidence: 99%

Canine prostatic cancer cell line (LuMa) with osteoblastic bone metastasis

Elshafae

Dirksen

Alasonyalilar-Demirer

et al. 2020

The Prostate

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Background: Osteoblastic bone metastasis represents the most common complication in men with prostate cancer (PCa). During progression and bone metastasis, PCa cells acquire properties similar to bone cells in a phenomenon called osteomimicry, which promotes their ability to metastasize, proliferate, and survive in the bone microenvironment. The mechanism of osteomimicry resulting in osteoblastic bone metastasis is unclear. Methods:We developed and characterized a novel canine prostatic cancer cell line (LuMa) that will be useful to investigate the relationship between osteoblastic bone metastasis and osteomimicry in PCa. The LuMa cell line was established from a primary prostate carcinoma of a 13-year old mixed breed castrated male dog. Cell proliferation and gene expression of LuMa were measured and compared to three other canine prostatic cancer cell lines (Probasco, Ace-1, and Leo) in vitro. The effect of LuMa cells on calvaria and murine preosteoblastic (MC3T3-E1) cells was measured by quantitative reverse-transcription polymerase chain reaction and alkaline phosphatase assay. LuMa cells were transduced with luciferase for monitoring in vivo tumor growth and metastasis using different inoculation routes (subcutaneous, intratibial [IT], and intracardiac [IC]). Xenograft tumors and metastases were evaluated using radiography and histopathology. Results: After left ventricular injection, LuMa cells metastasized to bone, brain, and adrenal glands. IT injections induced tumors with intramedullary new bone formation. LuMa cells had the highest messenger RNA levels of osteomimicry genes (RUNX2, RANKL, and Osteopontin [OPN]), CD44, E-cadherin, and MYOF compared to Ace-1, Probasco, and Leo cells. LuMa cells induced growth in calvaria defects and modulated gene expression in MC3T3-E1 cells. Conclusions: LuMa is a novel canine PCa cell line with osteomimicry and stemness properties. LuMa cells induced osteoblastic bone formation in vitro and in vivo.LuMa PCa cells will serve as an excellent model for studying the mechanisms of osteomimicry and osteoblastic bone and brain metastasis in prostate cancer. K E Y W O R D Sbone, canine, dog, metastasis, osteoblast, prostate cancer, tumor

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Review of Animal Models of Prostate Cancer Bone Metastasis

Cited by 20 publications

References 98 publications

Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer

Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer

Animal Models of Bone Metastasis

Canine prostatic cancer cell line (LuMa) with osteoblastic bone metastasis

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