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Clinical & Experimental Metastasis

, Volume 25, Issue 5, pp 581–590 | Cite as

Intraosseous injection of RM1 murine prostate cancer cells promotes rapid osteolysis and periosteal bone deposition

  • N. Patrick McCabe
  • Maria Madajka
  • Amit Vasanji
  • Tatiana V. Byzova
Research Paper

Abstract

The molecular mechanisms associated with prostate cancer (PCa) progression within bone remain a topic of intense investigation. With the availability of transgenic mouse strains, a model of PCa for use in immune competent/transgenic mice would be highly beneficial. This study was designed to explore the utility of RM1 mouse PCa cells in investigations of tumor:bone interactions. The efficacies of several implantation techniques were examined for reliably producing intra-bone RM1 tumor growth and bone lesion formation in immune competent mice. Longitudinal monitoring of bone remodeling and lesion phenotypes was conducted by microcomputed tomography (μCT) and histological analyses. Our results indicate that direct intrabone injections of RM1 cells are necessary for tumor growth within bone and direct implantation promotes the rapid development of osteolytic bone lesions with periosteal bone deposition post-cortical breach. In vitro, RM1 cells promote the proliferation of osteoblast (MC3T3-E1) and osteoclast (Raw264.7) progenitors in a dose dependent manner. Conditioned culture media from RM1 cells appears to promote earlier expression of genes/proteins associated with osteoblastic differentiation. While clearly stimulating osteoclast function in vivo, RM1 cells had little effect on differentiation and tartate resistant acid phosphatase (TRAP) expression by Raw264.7 cells. These data, coupled with in vivo μCT images, indicate the ability of RM1 cells to induce mixed, yet predominentally osteolytic, responses in bone and illustrate the potential of RM1 cells as a model of investigating prostate tumor:stroma interactions in immune competent/transgenic mice on a C57BL/6 background.

Keywords

Prostate cancer Bone Animal model Osteolytic Osteoblastic 

Notes

Acknowledgements

This work was supported by the following grants: DK060933/CA126847 to T.V. Byzova. N.P. McCabe is supported by a Ruth L. Kirschstein Research Service Award (NRSA) Individual Fellowship (5F32CA1172462); Cleveland Clinic Musculoskeletal Core Center funded in part by NIAMS Core Center Grant 1P30 AR-050953.

Supplementary material

10585_2008_9175_MOESM1_ESM.pdf (52 kb)
Supplemental Fig. 1. E0771 murine breast carcinoma cells produce strictly lytic responses following direct intratibial injection. (a) H&E stained section of tibia 21 days following injection of 1x104 cells. Arrowhead depicts region of corticle breach with adjacent soft tissue invasion by E0771 cells. Magnification of 5×. (b) Osteoclasts in resorption lacunae adjacent to tumor cells. Arrows indicate resorption lacunae. Magnification of 40×. (c) Isosurface volume of tibia 21 days following the injection of E0771 cells. Arrow indicates region of corticle erosion. (PDF 51 kb)

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • N. Patrick McCabe
    • 1
  • Maria Madajka
    • 1
  • Amit Vasanji
    • 2
  • Tatiana V. Byzova
    • 1
    • 3
  1. 1.Department of Molecular Cardiology, NB50The Cleveland Clinic Lerner Research InstituteClevelandUSA
  2. 2.Department of Biomedical EngineeringThe Cleveland Clinic Lerner Research InstituteClevelandUSA
  3. 3.The Cleveland ClinicTaussig Cancer CenterClevelandUSA

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