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

Simple Summary Bone metastasis is frequently complicated in patients with advanced solid cancers such as breast, prostate and lung cancers, and impairs their prognosis. Bone metastasis proceeds through the interaction between cancer cells and resident cells in bone. Among resident cells, osteoclasts are commonly activated in bone metastasis, and therefore, the drugs targeting osteoclast activation are frequently used to treat bone metastasis. However, their ineffectiveness to inhibit cancer cell growth in bone marrow, raises the possibility of the involvement of additional types of resident cells in bone metastasis. Cancer-associated fibroblasts (CAFs) are fibroblasts that accumulate in cancer tissues as well as metastatic organs including bone. Hence, we will discuss the potential roles of CAFs, which are emerging as an important cellular player in bone metastasis. 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.