A novel model of bone-metastatic prostate cancer in immunocompetent mice

Prostate. 2009 Nov 1;69(15):1613-23. doi: 10.1002/pros.21010.

Abstract

Background: Bone metastasis is a frequent and catastrophic consequence of prostate cancer for which only palliative treatment is available. Animal models of bone metastatic prostate cancer are necessary for understanding disease mechanisms but few models exist.

Methods: We have used the murine prostate carcinoma cell line RM1 to generate a bone metastatic model of prostate cancer. Repeated intracardiac injection of RM1 cells followed by isolation of cells from bone tumors has yielded a cell line with strong bone-metastatic potential, RM1 bone metastatic (BM).

Results: This cell line metastasizes to multiple bony sites in over 95% of injected C57BL/6 mice and is far less tropic to soft tissues. Bone tumors produced by the RM1(BM) cell line show no preference for particular skeletal sites as most bones are affected. Histology, and micro-computed tomography show that RM1(BM) cells form osteolytic tumors, but with evidence of osteoblastic changes. In vitro the RM1 cells express E-cadherin but not vimentin, do not form colonies in soft agar, are non-invasive but are more motile than the parent cell line.

Conclusions: This model provides a novel means for identifying cellular and molecular mechanisms that contribute to bone metastasis and allow for preclinical testing of therapies to prevent and treat tumor metastasis to bone. Finally as the syngeneic tumor cells are injected into immunocompetent mice, this model will provide a means to study interactions between the immune system, tumors and bone, and therapies that target such interactions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acid Phosphatase / blood
  • Animals
  • Bone Neoplasms / blood
  • Bone Neoplasms / immunology
  • Bone Neoplasms / secondary*
  • Cell Adhesion / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Disease Models, Animal
  • Histocytochemistry
  • Immunocompetence
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Osteocalcin / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology*
  • Tomography, X-Ray Computed

Substances

  • Osteocalcin
  • Acid Phosphatase