Abstract
While the skeleton is not the only organ where metastasis can occur, it is one of the preferred sites, with a significant impact in patients' quality of life. With the aim of delineating the cellular and molecular mechanisms of bone metastasis, numerous studies have been employed to identify any contributing factors that trigger cancer progression. One of the major limitations of studying cancer-bone metastasis is the multifaceted nature of the native bone environment and the lack of reliable, simple, and not expensive models that strictly mimic the biological processes occurring in vivo allowing a correct translation of results. Currently, with the growing acceptance of in vitro models as effective tools for studying cancer biology, three-dimensional (3D) models have emerged as a compromise between two-dimensional cultures of isolated cancer cells and the complexity of human cancer xenografts in immunocompromised animal hosts. This descriptive systematic literature review summarizes the current status of advanced and alternative 3D in vitro bone metastases models. We have also reviewed the strategies employed by researchers to set-up these models with special reference to recent promising developments trying to better replicate the complexity and heterogeneity of a human metastasis in situ, with an outlook at their use in medicine. All these aspects will greatly contribute to the existing knowledge on bone metastases, providing a specific link to clinical scenarios and thus making 3D in vitro bone metastasis models an attractive tool for multidisciplinary experts.
Highlights
Metastasis, defined as the spread and growth of tumor cells to distant organs, is a dejected consequence of many types of tumors, representing the most devastating attribute of cancer [1,2,3,4]
Our aim is to provide answers to questions such as: “Since bone is a complex environment containing many cell types, is it possible to study all the mechanisms of bone metastases in a 3D in vitro model?”, “What happens when bone metastatic cancer cells are added to a 3D in vitro model?”, “What kind of 3D in vitro model should be used and what model closely mimics the clinical scenario?”, “Are these models able to catalyze the development of new therapeutic interventions?”, “How much the proposed model closely reflects the data collected so far in clinical trials?” and “How much the proposed model can help in elucidating the mechanisms at the basis of bone invasion and metastasis?”
Given the growing interest in this field (PubMed citations for this topic have increased three-fold in the 2015-2010 period compared to 2005-2010), many stimulating ideas about the use and improvement of these 3D in vitro models have emerged in the last decade
Summary
Metastasis, defined as the spread and growth of tumor cells to distant organs, is a dejected consequence of many types of tumors, representing the most devastating attribute of cancer [1,2,3,4]. The process of cancer metastases, following tumor growth at the primary site of origin, involves intravasation and survival in the bloodstream, arrest, extravasation and establishment, by invasion and angiogenesis, at a distant site [17,18]. Tumor cells that metastasize in bone induce destructive osteolytic and/. Once bone metastases are present, patient survival is dramatically reduced. Most patients with metastatic bone disease survive for 6-48 months following diagnosis. The understanding of the cellular and molecular pathways involved in cancer-bone interaction and in metastasis treatment needs reliable models able to mimic the biological processes occurring in patients
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call