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

• Published in: Acta biomaterialia 2019-11, Vol.99, p.18-32
• Main Authors: González Díaz, Eva C., Sinha, Sauradeep, Avedian, Raffi S., Yang, Fan
• Format: Article
• Language: English
• Subjects: Biocompatible Materials; Biomaterials; Biomimetics; Bone cancer; Bone metastasis; Bone Neoplasms - pathology; Bone Neoplasms - secondary; Bone tumors; Bones; Breast; Breast cancer; Breast Neoplasms - pathology; Cell culture; Disease Progression; Drug screening; Female; Humans; Hydrogels - chemistry; Imaging, Three-Dimensional; Lung cancer; Male; Metastases; Metastasis; Neoplasia; Neoplasm Metastasis; Neoplasms; Prostate cancer; Prostatic Neoplasms - pathology; Spheroids, Cellular; Target recognition; Therapeutic applications; Three dimensional models; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds; Tumors
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2019.08.020

[Display omitted] 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. 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.