Use of FVB Myc-CaP cells as an immune competent, androgen receptor positive, mouse model of prostate cancer bone metastasis

Yu Wang; Mackenzie K Herroon; Steven P Zielske; Leigh Ellis; Izabela Podgorski; Russell S Taichman; Frank C Cackowski

doi:10.1016/j.jbo.2021.100386

Use of FVB Myc-CaP cells as an immune competent, androgen receptor positive, mouse model of prostate cancer bone metastasis

J Bone Oncol. 2021 Aug 18:30:100386. doi: 10.1016/j.jbo.2021.100386. eCollection 2021 Oct.

Authors

Yu Wang¹, Mackenzie K Herroon^{2

3}, Steven P Zielske³, Leigh Ellis⁴, Izabela Podgorski^{2

3}, Russell S Taichman^{1

5}, Frank C Cackowski^{3

6}

Affiliations

¹ Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
² Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.
³ Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, MI, USA.
⁴ Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁵ Department of Periodontology, University of Alabama at Birmingham School of Dentistry, Birmingham, AL, USA.
⁶ Department of Medicine, Division of Hematology, & Oncology, University of Michigan School of Medicine, Ann Arbor, MI, USA.

Abstract

Prostate cancer (PCa) metastasis research has been hamstrung by lack of animal models that closely resemble the disease present in most patients - that metastasize to bone, are dependent on the androgen receptor (AR), and grow in an immune competent host. Here, we adapt the Myc-CaP cell line for use as a PCa androgen dependent, immune competent bone metastases model and characterize the metastases. After injection into the left cardiac ventricle of syngeneic FVB/NJ mice, these cells formed bone metastases in the majority of animals; easily visible on H&E sections and confirmed by immunohistochemistry for Ar and epithelial cell adhesion molecule. Mediastinal tumors were also observed. We also labeled Myc-CaP cells with tdTomato, and confirmed the presence of cancer cells in bone by flow cytometry. To adapt the model to a bone predominant metastasis pattern and further examine the bone phenotype, we labeled the cells with luciferase, injected in the tibia and observed tumor formation only in tibia with a mixed osteolytic/osteoblastic phenotype. The presence of Myc-CaP tumors significantly increased tibia bone volume as compared to sham injected controls. The osteoclast marker, TRAcP-5b was not significantly changed in plasma from tibial tumor bearing animals vs. sham animals. However, conditioned media from Myc-CaP cells stimulated osteoclast formation in vitro from FVB/NJ mouse bone marrow. Overall, Myc-CaP cells injected in the left ventricle or tibia of syngeneic mice recapitulate key aspects of human metastatic PCa.

Keywords: Androgen receptor; Bone; Immune competent; Metastasis; Model system; Prostate cancer.

Abstract

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