Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer

Michelle L. Thompson, Juan M. Jimenez-Andrade, Stephane Chartier, James Tsai, Elizabeth A. Burton, Gaston Habets, Paul S. Lin, Brian L. West, Patrick W Mantyh

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Tumor cells frequently metastasize to bone where they can generate cancer-induced bone pain (CIBP) that can be difficult to fully control using available therapies. Here, we explored whether PLX3397, a high-affinity small molecular antagonist that binds to and inhibits phosphorylation of colony-stimulating factor-1 receptor, the tyrosine-protein kinase c-Kit, and the FMS-like tyrosine kinase 3, can reduce CIBP. These 3 targets all regulate the proliferation and function of a subset of the myeloid cells including macrophages, osteoclasts, and mast cells. Preliminary experiments show that PLX3397 attenuated inflammatory pain after formalin injection into the hind paw of the rat. As there is an inflammatory component in CIBP, involving macrophages and osteoclasts, the effect of PLX3397 was explored in a prostate model of CIBP where skeletal pain, cancer cell proliferation, tumor metastasis, and bone remodeling could be monitored in the same animal. Administration of PLX3397 was initiated on day 14 after prostate cancer cell injection when the tumor was well established, and tumor-induced bone remodeling was first evident. Over the next 6 weeks, sustained administration of PLX3397 attenuated CIBP behaviors by approximately 50% and was equally efficacious in reducing tumor cell growth, formation of new tumor colonies in bone, and pathological tumor-induced bone remodeling. Developing a better understanding of potential effects that analgesic therapies have on the tumor itself may allow the development of therapies that not only better control the pain but also positively impact disease progression and overall survival in patients with bone cancer.

Original languageEnglish (US)
Pages (from-to)1692-1702
Number of pages11
JournalPain
Volume156
Issue number9
DOIs
StatePublished - Sep 1 2015

Fingerprint

Bone Neoplasms
Cell Lineage
Disease Progression
Prostate
Pain
Bone Remodeling
Neoplasms
Osteoclasts
Protein-Tyrosine Kinases
Prostatic Neoplasms
Colony-Stimulating Factor Receptors
Macrophages
Bone and Bones
Injections
Macrophage Colony-Stimulating Factor
Myeloid Cells
Mast Cells
Formaldehyde
Analgesics
Therapeutics

Keywords

  • Disease progression
  • Macrophage
  • Mast cell
  • Osteoblast
  • Osteoclast
  • Pain
  • Survival

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine
  • Neurology
  • Pharmacology

Cite this

Thompson, M. L., Jimenez-Andrade, J. M., Chartier, S., Tsai, J., Burton, E. A., Habets, G., ... Mantyh, P. W. (2015). Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer. Pain, 156(9), 1692-1702. https://doi.org/10.1097/j.pain.0000000000000228

Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer. / Thompson, Michelle L.; Jimenez-Andrade, Juan M.; Chartier, Stephane; Tsai, James; Burton, Elizabeth A.; Habets, Gaston; Lin, Paul S.; West, Brian L.; Mantyh, Patrick W.

In: Pain, Vol. 156, No. 9, 01.09.2015, p. 1692-1702.

Research output: Contribution to journalArticle

Thompson, ML, Jimenez-Andrade, JM, Chartier, S, Tsai, J, Burton, EA, Habets, G, Lin, PS, West, BL & Mantyh, PW 2015, 'Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer', Pain, vol. 156, no. 9, pp. 1692-1702. https://doi.org/10.1097/j.pain.0000000000000228
Thompson ML, Jimenez-Andrade JM, Chartier S, Tsai J, Burton EA, Habets G et al. Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer. Pain. 2015 Sep 1;156(9):1692-1702. https://doi.org/10.1097/j.pain.0000000000000228
Thompson, Michelle L. ; Jimenez-Andrade, Juan M. ; Chartier, Stephane ; Tsai, James ; Burton, Elizabeth A. ; Habets, Gaston ; Lin, Paul S. ; West, Brian L. ; Mantyh, Patrick W. / Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer. In: Pain. 2015 ; Vol. 156, No. 9. pp. 1692-1702.
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