The Role of Bone Stem Cell Niches in Bone Metastasis

Roberto Tamma,Domenico Ribatti,Tiziana Annese

doi:10.3390/app10217713

Roberto Tamma, Domenico Ribatti + Show 1 more

Open Access

https://doi.org/10.3390/app10217713

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Abstract

In post-natal life, stem cells contribute to the preservation of many tissues. In adults, stem cells remain localized, in particular, specialized microanatomical areas named as niches, which are crucial in the control of stem cell quiescence and activity through the production of many regulatory signals. Bone physiologically includes both the endosteal niche and the vascular niche, which are involved in the attraction, retention and release of the residing stem cells during the formation of new vessels as well as in the control of the differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts. In tumors, cancer cells are able to take control of the niches to support all the stages of the tumorigenesis, transforming them in the so-called pre-metastatic and metastatic niches. Hence, there is emerging importance of the interactions between cancer cells, bone cells and niches in driving metastatic progression. This review article summarizes the literature data concerning the role of bone vascular and endosteal niches in the regulation of bone metastasis, focusing on their cellular and molecular interactions and the potential therapeutic approaches.

Highlights

Metastasis is a multi-phase process that requires the detachment of cancer cells from the primary tumor, their migration through the adjacent tissue, entering the bloodstream and reaching the distant organs where they find the microenvironment suitable for surviving and proliferating [1,2].Currently it is believed that metastatic process is responsible for a great percentage of cancer-related death [3].Bone is the third most common site of metastatic occurrence after lung and liver
It is estimated that nearly 70% of breast cancer patients and 90% of prostate cancer patients that die from disease have bone metastases but other common bone metastasizing cancers include the bladder, renal, thyroid, sarcoma and lymphomas [5]
OPN is involved in the regulation of each critical step of the process of metastasis [57,58], and correlation has been established between OPN and the metastatic spread of breast, prostate, colon and liver cancers [48,49] (Figure 2)

Summary

Introduction

Metastasis is a multi-phase process that requires the detachment of cancer cells from the primary tumor, their migration through the adjacent tissue, entering the bloodstream and reaching the distant organs where they find the microenvironment suitable for surviving and proliferating [1,2]. Most bone metastases originate from prostate, breast and lung cancer. It is estimated that nearly 70% of breast cancer patients and 90% of prostate cancer patients that die from disease have bone metastases but other common bone metastasizing cancers include the bladder, renal, thyroid, sarcoma and lymphomas [5]. In this short review article, we try to elucidate some aspects about the interactions between metastatic cells and the microenvironment present in bone staminal niches because this could be very useful to elaborate strategies that can target these interactions and prevent or eradicate metastatic disease

Pre-Metastatic Niche

Bone Staminal Niche and Metastasis

Findings

Concluding Remarks and Therapeutic Perspectives