Osteoblasts Are the Centerpiece of the Metastatic Bone Microenvironment

Hyo Min Jeong, Sun Wook Cho, Serk In Park, Hyo Min Jeong, Sun Wook Cho, Serk In Park

Abstract

The tumor microenvironment is comprised of diverse stromal cell populations in addition to tumor cells. Increasing evidence now clearly supports the role of microenvironment stromal cells in tumor progression and metastasis, yet the regulatory mechanisms and interactions among tumor and stromal cells remain to be elucidated. Bone metastasis is the major problem in many types of human malignancies including prostate, breast and lung cancers, and the biological basis of bone metastasis let alone curative approaches are largely undetermined. Among the many types of stromal cells in bone, osteoblasts are shown to be an important player. In this regard, osteoblasts are a key target cell type in the development of bone metastasis, but there are currently no drugs or therapeutic approaches are available that specifically target osteoblasts. This review paper summarizes the current knowledge on osteoblasts in the metastatic tumor microenvironment, aiming to provide clues and directions for future research endeavor.

Keywords: Bone and bones; Microenvironment; Neoplasm metastasis; Neoplasms; Osteoblasts; Osteoclasts.

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1. PC-3, metastatic human prostate cancer…
Fig. 1. PC-3, metastatic human prostate cancer cells, were injected in to the proximal tibia of male athymic nude mice [57]. Tumors (Tu) were harvested after 3 weeks, followed by fixation, decalcification, sectioning, and modified H&E staining (showing bone matrices in orange) [58]. Osteoblasts (Obl), physiologically unilayer cells, formed multiple layers (indicating proliferation; bracket), with woven bone (WB; newly formed bone; solid arrow) formation around the tumor tissue (dotted line). Lamellar bone (LB; remodeled bone) and osteoclasts (Ocl) are clearly visible. This data supports that osteoblasts are actively respond to metastatic tumor cells, and potentially play important roles in bone metastasis. BM, bone marrow.

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