Tissue-engineered 3D models for elucidating primary and metastatic bone cancer progression

Acta Biomater. 2019 Nov:99:18-32. doi: 10.1016/j.actbio.2019.08.020. Epub 2019 Aug 13.

Abstract

Malignant bone tumors are aggressive neoplasms which arise from bone tissue or as a result of metastasis. The most prevalent types of cancer, such as breast, prostate, and lung cancer, all preferentially metastasize to bone, yet the role of the bone niche in promoting cancer progression remains poorly understood. Tissue engineering has the potential to bridge this knowledge gap by providing 3D in vitro systems that can be specifically designed to mimic key properties of the bone niche in a more physiologically relevant context than standard 2D culture. Elucidating the crucial components of the bone niche that recruit metastatic cells, support tumor growth, and promote cancer-induced destruction of bone tissue would support efforts for preventing and treating these devastating malignancies. In this review, we summarize recent efforts focused on developing in vitro 3D models of primary bone cancer and bone metastasis using tissue engineering approaches. Such 3D in vitro models can enable the identification of effective therapeutic targets and facilitate high-throughput drug screening to effectively treat bone cancers. STATEMENT OF SIGNIFICANCE: Biomaterials-based 3D culture have been traditionally used for tissue regeneration. Recent research harnessed biomaterials to create 3D in vitro cancer models, with demonstrated advantages over conventional 2D culture in recapitulating tumor progression and drug response in vivo. However, previous work has been largely limited to modeling soft tissue cancer, such as breast cancer and brain cancer. Unlike soft tissues, bone is characterized with high stiffness and mineral content. Primary bone cancer affects mostly children with poor treatment outcomes, and bone is the most common site of cancer metastasis. Here we summarize emerging efforts on engineering 3D bone cancer models using tissue engineering approaches, and future directions needed to further advance this relatively new research area.

Keywords: Biomaterials; Bone cancer; Bone metastasis; Tissue engineering.

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.
  • Review

MeSH terms

  • Biocompatible Materials
  • Biomimetics
  • Bone Neoplasms / pathology*
  • Bone Neoplasms / secondary*
  • Breast Neoplasms / pathology
  • Disease Progression
  • Female
  • Humans
  • Hydrogels / chemistry
  • Imaging, Three-Dimensional
  • Male
  • Neoplasm Metastasis
  • Prostatic Neoplasms / pathology
  • Spheroids, Cellular
  • Tissue Engineering / methods*
  • Tissue Scaffolds

Substances

  • Biocompatible Materials
  • Hydrogels