Improving orthotopic mouse models of patient-derived breast cancer brain metastases by a modified intracarotid injection method

Sci Rep. 2019 Jan 24;9(1):622. doi: 10.1038/s41598-018-36874-3.

Abstract

Breast cancer brain metastasis (BCBM) remains a major clinical problem. Approximately 10-16% of patients with breast cancer develop brain metastases (BCBM). However, no systemic therapy has gained regulatory approval for the specific treatment of BCBM and this remains an area of persistent, unmet medical need. Rapid, predictive and clinically-relevant animal models are critical to study the biology of brain metastases and to identify effective therapeutic approaches for patients with BCBM. Here, we describe a method for efficient establishment of orthotopic mouse models of patient-derived brain metastases via an improved intracarotid injection protocol that permits tumor cell growth in the unique brain microenvironment without compromising the blood-brain barrier (BBB). We demonstrate that our newly improved models of patient-derived brain metastases recapitulate the histologic, molecular, and genetic characteristics of their matched patient tumor specimens and thus represent a potentially powerful tool for pre-clinical and translational research.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Blood-Brain Barrier / metabolism
  • Brain Neoplasms / etiology*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Breast Neoplasms / complications*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Disease Models, Animal
  • Exome Sequencing
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Mice
  • Tumor Microenvironment / physiology

Substances

  • Biomarkers, Tumor