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Review
. 2020 Oct 9;12(10):2896.
doi: 10.3390/cancers12102896.

Emergence of Cancer-Associated Fibroblasts as an Indispensable Cellular Player in Bone Metastasis Process

Naofumi Mukaida  1 , Di Zhang  1 , So-Ichiro Sasaki  1
Affiliations
Review

Emergence of Cancer-Associated Fibroblasts as an Indispensable Cellular Player in Bone Metastasis Process

Naofumi Mukaida et al. Cancers (Basel). .

Abstract

Bone metastasis is frequently complicated in patients with advanced solid cancers such as breast, prostate and lung cancers, and impairs patients' quality of life and prognosis. At the first step of bone metastasis, cancer cells adhere to the endothelium in bone marrow and survive in a dormant state by utilizing hematopoietic niches present therein. Once a dormant stage is disturbed, cancer cells grow through the interaction with various bone marrow resident cells, particularly osteoclasts and osteoblasts. Consequently, osteoclast activation is a hallmark of bone metastasis. As a consequence, the drugs targeting osteoclast activation are frequently used to treat bone metastasis but are not effective to inhibit cancer cell growth in bone marrow. Thus, additional types of resident cells are presumed to contribute to cancer cell growth in bone metastasis sites. Cancer-associated fibroblasts (CAFs) are fibroblasts that accumulate in cancer tissues and can have diverse roles in cancer progression and metastasis. Given the presence of CAFs in bone metastasis sites, CAFs are emerging as an important cellular player in bone metastasis. Hence, in this review, we will discuss the potential roles of CAFs in tumor progression, particularly bone metastasis.

Keywords: bone metastasis; cancer-associated fibroblast; fibroblast; mesenchymal stem cell; myofibroblast.

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Conflict of interest statement

The authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Ontogeny and phenotypes of cancer-associated fibroblasts (CAFs) and myofibroblasts. Parentheses indicate representative surface makers of each cell population. Used abbreviations: PECAM-1, platelet endothelial cell adhesion molecule-1; UCP1, uncoupling protein 1.
Figure 2
Figure 2
Bone remodeling and vicious cycle in bone metastasis.
Figure 3
Figure 3
Functions of CAFs in tumor progression involved in metastasis.
Figure 4
Figure 4
Presumed roles of CAFs in bone metastasis processes.
See this image and copyright information in PMC

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