Microenvironment engineering of osteoblastic bone metastases reveals osteomimicry of patient-derived prostate cancer xenografts

Biomaterials. 2019 Nov;220:119402. doi: 10.1016/j.biomaterials.2019.119402. Epub 2019 Jul 31.

Abstract

Representative in vitro models that mimic the native bone tumor microenvironment are warranted to support the development of more successful treatments for bone metastases. Here, we have developed a primary cell 3D model consisting of a human osteoblast-derived tissue-engineered construct (hOTEC) indirectly co-cultured with patient-derived prostate cancer xenografts (PDXs), in order to study molecular interactions in a patient-derived microenvironment context. The engineered biomimetic microenvironment had high mineralization and embedded osteocytes, and supported a high degree of cancer cell osteomimicry at the gene, protein and mineralization levels when co-cultured with prostate cancer PDXs from a lymph node metastasis (LuCaP35) and bone metastasis (BM18) from patients with primary prostate cancer. This fully patient-derived model is a promising tool for the assessment of new molecular mechanisms and as a personalized pre-clinical platform for therapy testing for patients with prostate cancer bone metastases.

Keywords: Bone metastasis; Cancer model; Osteocyte; Osteomimicry; Patient-derived xenograft; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Biomimetics*
  • Bone Matrix / metabolism
  • Bone Neoplasms / genetics
  • Bone Neoplasms / secondary*
  • Bone and Bones / pathology
  • Bone and Bones / ultrastructure
  • Calcification, Physiologic
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Extracellular Matrix / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice, Inbred NOD
  • Osteoblasts / pathology*
  • Osteocytes / metabolism
  • Osteocytes / ultrastructure
  • Prostatic Neoplasms / pathology*
  • Tissue Engineering*
  • Tissue Scaffolds / chemistry
  • Tumor Microenvironment*
  • Xenograft Model Antitumor Assays*