Canine prostate cancer cell line (Probasco) produces osteoblastic metastases in vivo

Simmons, Jessica K.; Dirksen, Wessel P.; Hildreth, Blake E.; Dorr, Carlee; Williams, Christina; Thomas, Rachael; Breen, Matthew; Toribio, Ramiro E.; Rosol, Thomas J.

doi:10.1002/pros.22838

Cited by 31 publications

(41 citation statements)

References 51 publications

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“…122,135 It is a relatively simple technique and often causes limited morbidity to the animal. Also, neonatal mouse vertebrae (vossicles) or fragments of fetal human bone can be implanted subcutaneously in mice and used as a substrate for cancer cells.…”

Section: In Vivo Injection Techniques Used To Induce Bone Metastasismentioning

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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Section: In Vivo Injection Techniques Used To Induce Bone Metastasismentioning

confidence: 99%

Animal Models of Bone Metastasis

et al. 2015

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“…Because bone is the most favored metastatic site in prostate cancer cases, we investigated the in vivo antimetastatic efficacy of PI3Kb inhibitor GSK2636771 and PI3Kd inhibitor CAL101 on a well-known experimental metastasis model (32)(33)(34) by mCT and histologic analysis of bone lesions. Oral administration of GSK2636771 or CAL101 for 42 d significantly increased bone volume and density without apparent weight loss ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…We also investigated the in vivo antimetastatic effect of the oral PI3Kb inhibitor GSK2636771 and PI3Kd inhibitor CAL101 by using an experimental metastasis model (32)(33)(34), which was developed by intratibia injection of prostate cancer DU145 cells in nude mice. Although such a model does not represent the complete metastasis process, it is usable for investigation of the ability of tumor cells to colonize the bone and for tumor-bone interactions, which are essential for bone (33,34).…”

Section: Pi3kb and Pi3kd Isoform Inhibitors Showed Antimetastatic Effmentioning

confidence: 99%

Phosphatidylinositol 3‐kinase β and β isoforms play key roles in metastasis of prostate cancer DU145 cells

et al. 2018

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Metastasis is the main cause of the lethality of prostate cancer. Class I phosphatidylinositol 3‐kinases (PI3Ks), which contain 4 isoforms, α, β, δ, and γ, are known to play important roles in cell growth, migration, invasion, and so on. However, the respective role of each PI3K isoform in cancer cell migration and invasion remains unknown. In a study that aimed to elucidate the respective role of the 4 PI3K isoforms, we investigated the change in migratory and invasive ability of DU145 cells after treatment with each PI3K isoform‐specific inhibitor. Both migration and invasion of DU145 cells were potently blocked by each of the PI3Kβ inhibitors (GSK2636771 and TGX221) and PI3Kδ inhibitors (CAL101 and IC87114) while not obviously affected by PI3Kα inhibitor BYL719 or PI3Kγ inhibitor AS252424. Furthermore, knocking down PI3Kβ or PI3Kδ isoform led to a significant decrease in migration of DU145. The results suggest that PI3Kβ and PI3Kδ play key roles in prostate cancer cell migration, while PI3Kα and PI3Kγ might be redundant. Oral administration of GSK2636771 (100 mg/kg) and CAL101 (30 mg/kg) inhibited tumor growth in bone, an experimental model by intratibia injection of DU145 cells, with improved bone structure and bone mineral density analyzed by micro‐computed tomography. Tissue staining indicated reduction of metastatic DU145 cells and osteoclasts in the bones of GSK2636771‐ and CAL101‐treated mice compared to the untreated group. In summary, our results indicated the distinct roles of 4 PI3K isoforms in the migration of prostate cancer DU145 cells, and they demonstrated the in vitro and in vivo antimetastatic effect of PI3K‐isoform specific inhibitors, most of which are in clinical trials.—Zhang, Z., Liu, J., Wang, Y., Tan, X., Zhao, W., Xing, X., Qiu, Y., Wang, R., Jin, M., Fan, G., Zhang, P., Zhong, Y., Kong, D. Phosphatidylinositol 3‐kinase β and δ isoforms play key roles in metastasis of prostate cancer DU145 cells. FASEB J. 32, 5967–5975 (2018). http://www.fasebj.org

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“…Calvaria were removed from 5 to 12‐day old nude mouse pups (NCr‐nu/nu) supplied by the OSU Comprehensive Cancer Center (OSUCCC) Target Validation Shared Resource (TVSR). Four canine prostate cancer cell lines were used in this study including Ace‐1, 27 Probasco, 33 Leo, 34 and LuMa (available from ABM Inc, Vancouver, Canada).…”

Section: Methodsmentioning

confidence: 99%

“…These include Ace‐1, Probasco, LuCAP‐23.1, and MDA‐PCa 2a & b. 27‐33 In this study, we have established and characterized a novel canine prostatic cell line (LuMa) that has unique osteomimicry properties, stem cell and invasive characteristics, and induces osteoblastic bone metastases in nude mice. These properties demonstrate that LuMa cells will be a valuable model in prostate cancer research.…”

Section: Introductionmentioning

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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Canine prostate cancer cell line (Probasco) produces osteoblastic metastases in vivo

Cited by 31 publications

References 51 publications

Animal Models of Bone Metastasis

Animal Models of Bone Metastasis

Phosphatidylinositol 3‐kinase β and β isoforms play key roles in metastasis of prostate cancer DU145 cells

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

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