Prostate cancer cells induce osteoblastic differentiation via semaphorin 3A

Liu, Fuzhou; Sui, Weiwei; Qiu, Hao; Hu, Xu; Zhang, Chao; Chu, Tongwei

doi:10.1002/pros.22923

Cited by 19 publications

(11 citation statements)

References 46 publications

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“…Liu et al. showed that osteoblastic differentiation was induced after osteoprogenitor cells were incubated with the conditioned media from PCa cells . In this study, we identified proteins involved in osteoblast differentiation to be associated with advanced PCa grades, proteins that can be further explored in the context of bone metastasis and bone damage induced by PCa cells.…”

Section: Discussionmentioning

confidence: 76%

Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia

et al. 2019

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The histology‐based Gleason score (GS) of prostate cancer (PCa) tissue biopsy is the most accurate predictor of disease aggressiveness and an important measure to guide treatment strategies and patient management. The variability associated with PCa tumor sampling and the subjective determination of the GS are challenges that limit accurate diagnostication and prognostication. Thus, novel molecular signatures are needed to distinguish between indolent and aggressive forms of PCa for better patient management and outcomes. Herein, label‐free LC‐MS/MS proteomics is used to profile the proteome of 50 PCa tissues spanning five grade groups (n = 10 per group) relative to tissues from individuals with benign prostatic hyperplasia (BPH). Over 2000 proteins are identified albeit at different levels between and within the patient groups, revealing biological processes associated with specific grades. A panel of 11 prostate‐derived proteins including IGKV3D‐20, RNASET2, TACC2, ANXA7, LMOD1, PRCP, GYG1, NDUFV1, H1FX, APOBEC3C, and CTSZ display the potential to stratify patients from low and high PCa grade groups. Parallel reaction monitoring of the same sample cohort validate the differential expression of LMOD1, GYG1, IGKV3D‐20, and RNASET2. The four proteins associated with low and high PCa grades reported here warrant further exploration as candidate biomarkers for PCa aggressiveness.

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Section: Discussionmentioning

confidence: 76%

Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia

et al. 2019

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“…In metastatic PCa, the semaphorin/plexin axis is not well studied, although there are hints of such an interaction in the literature. Multiple PCa cells express and release semaphorin 3A (Sema3A) to encourage osteoblastic differentiation of pre-osteoblastic MC3T3-E1 cells 40 . Class III semaphorins differentially affect PCa cells, in that Sema3A causes deadhesion and indolence and Sema3C overexpression produces more aggressive phenotypes 35 .…”

Section: Discussionmentioning

confidence: 99%

“…Semaphorins are a class of extracellular signaling molecules that provide cell guidance cues by modifying adhesion and motility 25 . Several PCa cells express Sema3A and its receptor neuropilin-1 that in turn binds to multiple plexins 40 , 50 . Plexins have an intracellular portion with Ras-GAP (guanosine triphosphate (GTP)ase activation protein) activity.…”

Section: Discussionmentioning

confidence: 99%

Matrilysin/MMP-7 Cleavage of Perlecan/HSPG2 Complexed with Semaphorin 3A Supports FAK-Mediated Stromal Invasion by Prostate Cancer Cells

Grindel

Martinez

Tellman

et al. 2018

Sci Rep

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Interrupting the interplay between cancer cells and extracellular matrix (ECM) is a strategy to halt tumor progression and stromal invasion. Perlecan/heparan sulfate proteoglycan 2 (HSPG2) is an extracellular proteoglycan that orchestrates tumor angiogenesis, proliferation, differentiation and invasion. Metastatic prostate cancer (PCa) cells degrade perlecan-rich tissue borders to reach bone, including the basement membrane, vasculature, reactive stromal matrix and bone marrow. Domain IV-3, perlecan’s last 7 immunoglobulin repeats, mimics native proteoglycan by promoting tumoroid formation. This is reversed by matrilysin/matrix metalloproteinase-7 (MMP-7) cleavage to favor cell dispersion and tumoroid dyscohesion. Both perlecan and Domain IV-3 induced a strong focal adhesion kinase (FAK) dephosphorylation/deactivation. MMP-7 cleavage of perlecan reversed this, with FAK in dispersed tumoroids becoming phosphorylated/activated with metastatic phenotype. We demonstrated Domain IV-3 interacts with the axon guidance protein semaphorin 3A (Sema3A) on PCa cells to deactivate pro-metastatic FAK. Sema3A antibody mimicked the Domain IV-3 clustering activity. Direct binding experiments showed Domain IV-3 binds Sema3A. Knockdown of Sema3A prevented Domain IV-3-induced tumoroid formation and Sema3A was sensitive to MMP-7 proteolysis. The perlecan-Sema3A complex abrogates FAK activity and stabilizes PCa cell interactions. MMP-7 expressing cells destroy the complex to initiate metastasis, destroy perlecan-rich borders, and favor invasion and progression to lethal bone disease.

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“…However, physiological condition of postmenopausal women was different from OVX rats, so that prediction of the effect of SEMA3A in human via results from this study should be made cautiously. It should be pointed out that observation time of 8 weeks merely revealed results at the early stages of implant healing, and longer observation time was needed in future studies for the evaluation of long‐term efficiency and safety of SEMA3A considering its multiple effects …”

Section: Discussionmentioning

confidence: 99%

“…It should be pointed out that observation time of 8 weeks merely revealed results at the early stages of implant healing, and longer observation time was needed in future studies for the evaluation of long-term efficiency and safety of SEMA3A considering its multiple effects. [18][19][20]…”

Section: Discussionmentioning

confidence: 99%

SEMA3A suspended in matrigel improves titanium implant fixation in ovariectomized rats

Liu

et al. 2016

J. Biomed. Mater. Res.

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The aim of this study was to evaluate the effect of SEMA3A released from matrigel on implant fixation in ovariectomized (OVX) rats. Sixty female rats were subjected to bilateral ovariectomy. Twelve weeks later, rats were randomly divided into three groups according to implants they accepted: (1) Control, implants with distilled water; (2) Matrigel, implants with matrigel coating; (3) Matrigel + SEMA3A, implants with coating of SEMA3A suspended in matrigel. Implants were inserted in metaphysis of proximal tibiae in all animas bilaterally. In vitro release of SEMA3A was tested using enzyme linked immunosorbent assay. In vitro release of SEMA3A was detectable during the first 10 days, and a burst release of was observed during the first 3 days. No significant difference was observed between Control and Matrigel group. The protective effects of SEMA3A in matrigel on peri-implant bone, implant osseointegration and fixation was confirmed. Compared to matrigel alone, SEMA3A suspended in matrigel increased percent bone volume by 88.7% and 83.3% (p < 0.01), bone-to-implant contact ratio by 148.9% (p < 0.01), and 24.8% (p < 0.05), the maximal push-out force by 149.3% and 209.2% (p < 0.01) at 4 and 8 weeks after implant insertion, respectively. Surface modification with SEMA3A suspended in matrigel improved implant osseointegration and fixation in the proximal tibiae of OVX rats. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2060-2065, 2017.

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Prostate cancer cells induce osteoblastic differentiation via semaphorin 3A

Abstract: Our results suggest that prostate cancer-induced osteoblastic differentiation is at least partially mediated by Sema 3A, and may be regulated by the β-catenin signalling pathway. Sema 3A may represent a novel target for treatment of prostate cancer-induced osteoblastic lesions.

Cited by 19 publications

References 46 publications

Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia

Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia

Matrilysin/MMP-7 Cleavage of Perlecan/HSPG2 Complexed with Semaphorin 3A Supports FAK-Mediated Stromal Invasion by Prostate Cancer Cells

SEMA3A suspended in matrigel improves titanium implant fixation in ovariectomized rats

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