Osteoblast‐derived factors promote metastatic potential in human prostate cancer cells, in part via non‐canonical transforming growth factor β (TGFβ) signaling

Karlsson, Terese; Sundar, Reshma; Widmark, Anders; Landström, Maréne; Persson, Emma

doi:10.1002/pros.23489

Cited by 15 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is becoming increasingly evident that osteoblasts in the bone microenvironment play vital roles in cancer cell progression in bone [19,[32][33][34][35][36]. According to one study that used dynamic longitudinal imaging and intravital microscopy, osteoblast cells in the endosteal niche suppressed multiple myeloma cancer cell proliferation and maintained bone-disseminated cancer cells in a dormant state during early disease [104].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…It is becoming increasingly evident that osteoblasts in the bone microenvironment play vital roles in cancer cell attraction [34,35], maintenance [33], and survival [19,32,36] during cancer progression in the bone. It was demonstrated that osteoblast-derived TGF-beta increased PC-3U prostate cancer cell migration [35]. Furthermore, osteoblast-derived CXCL12 mediated bone metastatic prostate cancer progression via binding of its receptor CXCR4 on the cancer cells [11,34,37,38].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Osteoblasts are “educated” by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment

et al. 2019

View full text Add to dashboard Cite

Introduction: In a cancer-free environment in the adult, the skeleton continuously undergoes remodeling. Boneresorbing osteoclasts excavate erosion cavities, and bone-depositing osteoblasts synthesize osteoid matrix that forms new bone, with no net bone gain or loss. When metastatic breast cancer cells invade the bone, this balance is disrupted. Patients with bone metastatic breast cancer frequently suffer from osteolytic bone lesions that elicit severe bone pain and fractures. Bisphosphonate treatments are not curative. Under ideal circumstances, osteoblasts would synthesize new matrix to fill in erosion cavities caused by osteoclasts, but this is not what occurs. Our prior evidence demonstrated that osteoblasts are diverted from laying down bone matrix to producing cytokines that facilitate breast cancer cell maintenance in late-stage disease. Here, we have new evidence to suggest that there are subpopulations of osteoblasts in the tumor niche as evidenced by their protein marker expression that have distinct roles in tumor progression in the bone. Methods: Tumor-bearing tibia of mice was interrogated by immunofluorescent staining for the presence of osteoblasts and alterations in niche protein expression. De-identified tissue from patients with bone metastatic breast cancer was analyzed for osteoblast subpopulations via multi-plex immunofluorescent staining. Effects of breast cancer cells on osteoblasts were recapitulated in vitro by osteoblast exposure to breast cancer-conditioned medium. Triplenegative and estrogen receptor-positive breast cancer proliferation, cell cycle, and p21 expression were assessed upon contact with "educated" osteoblasts. Results: A subpopulation of osteoblasts was identified in the bone tumor microenvironment in vivo of both humans and mice with bone metastatic breast cancer that express RUNX2/OCN/OPN but is negative for IL-6 and alpha-smooth muscle actin. These tumor "educated" osteoblasts (EOs) have altered properties compared to "uneducated" osteoblasts and suppress both triple-negative and estrogen receptor-positive breast cancer cell proliferation and increase cancer cell p21 expression. EO effects on breast cancer proliferation were mediated by NOV and decorin. Importantly, the presence of EO cells in the tibia of mice bearing tumors led to increased amounts of alkaline phosphatase and suppressed the expression of inflammatory cytokines in vivo. Conclusions: Our work reveals that there is a subpopulation of osteoblasts in the bone tumor microenvironment that demonstrate a functional role in retarding breast cancer cell growth.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Osteoblasts are “educated” by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Previews secrete factors such as TGFb, which are deposited into the mineralized bone matrix and can induce the metastatic potential of prostate cancer cells (Karlsson et al, 2018). Osteoblasts secrete factors (Kinder et al, 2008) and also differentiate into osteocytes, both of which can initiate osteoclastogenesis.…”

Section: Cell Metabolismmentioning

confidence: 99%

A “Connexin” Responsible for the Fatal Attraction of Cancer to Bone

2019

View full text Add to dashboard Cite

show abstract

“…Bone sialoprotein, which is a major glycoprotein, is regulated by TGF-β through β-catenin signaling [31]. Recently, it has also been reported that osteoblast-derived soluble factors, including TGF-β, indeed promote metastatic potential in prostate cancer cells, and the effect by TGF-β is, at least partly, mediated by noncanonical TRAF6-dependent signaling [32]. …”

Section: Tgf-β Exists In Bone Tissue and Is Implicated In Bone Metmentioning

confidence: 99%

TGF-Beta Signaling in Bone with Chronic Kidney Disease

Iwasaki

Yamato

Fukagawa

2018

IJMS

View full text Add to dashboard Cite

Transforming growth factor (TGF)-β signaling is not only important in skeletal development, but also essential in bone remodeling in adult bone. The bone remodeling process involves integrated cell activities induced by multiple stimuli to balance bone resorption and bone formation. TGF-β plays a role in bone remodeling by coordinating cell activities to maintain bone homeostasis. However, mineral metabolism disturbance in chronic kidney disease (CKD) results in abnormal bone remodeling, which leads to ectopic calcification in CKD. High circulating levels of humoral factors such as parathyroid hormone, fibroblast growth factor 23, and Wnt inhibitors modulate bone remodeling in CKD. Several reports have revealed that TGF-β is involved in the production and functions of these factors in bone. TGF-β may act as a factor that mediates abnormal bone remodeling in CKD.

show abstract

Osteoblast‐derived factors promote metastatic potential in human prostate cancer cells, in part via non‐canonical transforming growth factor β (TGFβ) signaling

Abstract: These findings suggests that factors secreted from osteoblasts, including TGFβ, can induce several cellular traits involved in metastatic potential of PC-3U cells, further strengthening the role for bone cells to promote metastatic tumor cell behavior.

Cited by 15 publications

References 27 publications

Osteoblasts are “educated” by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment

Osteoblasts are “educated” by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment

A “Connexin” Responsible for the Fatal Attraction of Cancer to Bone

TGF-Beta Signaling in Bone with Chronic Kidney Disease

Contact Info

Product

Resources

About