Oncogenic role of sFRP2 in P53-mutant osteosarcoma development via autocrine and paracrine mechanism

Kim, Huen Suk; Yoo, Seungyeul; Bernitz, Jeffrey; Yuan, Ye; Gomes, Andreia; Daniel, Michael G.; Su, Jie; Demicco, Elizabeth G.; Zhu, Jun; Moore, Kateri; Lee, Dung‐Fang; Lemischka, Ihor R.; Schaniel, Christoph

doi:10.1101/246454

Cited by 6 publications

(7 citation statements)

References 95 publications

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“…In a follow up-study we identified SFRP2 as an autocrine and paracrine factor involved in P53 mutation-mediated osteosarcomagenesis. Using genome-editing we confirmed a correlation between various P53 mutations and increased SFRP2 expression in iPSC and embryonic stem cell derived osteoblasts ( 54 ) and Kim et al (under review).…”

Section: Genome Editingsupporting

confidence: 71%

Modeling Hematological Diseases and Cancer With Patient-Specific Induced Pluripotent Stem Cells

Kim

Schaniel

2018

Front. Immunol.

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The advent of induced pluripotent stem cells (iPSCs) together with recent advances in genome editing, microphysiological systems, tissue engineering and xenograft models present new opportunities for the investigation of hematological diseases and cancer in a patient-specific context. Here we review the progress in the field and discuss the advantages, limitations, and challenges of iPSC-based malignancy modeling. We will also discuss the use of iPSCs and its derivatives as cellular sources for drug target identification, drug development and evaluation of pharmacological responses.

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Section: Genome Editingsupporting

confidence: 71%

Modeling Hematological Diseases and Cancer With Patient-Specific Induced Pluripotent Stem Cells

Kim

Schaniel

2018

Front. Immunol.

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“…On the other hand, inhibition of SFRP2, FoXM1 or CYR61 suppresses the tumorigenic process. This demonstrates that the oncogenic role of SFRP2 in OS development is due to its ability to induce oncogenic molecules such as FOXM1 and CYR61 in the presence of mutations in the TP53 gene (44).…”

Section: Role Of Dna Changesmentioning

confidence: 88%

Biology and pathogenesis of human osteosarcoma (Review)

Azevedo¹,

Fernandes

et al. 2019

Oncol Lett

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Osteosarcoma (OS) is a bone tumor of mesenchymal origin, most frequently occurring during the rapid growth phase of long bones, and usually located in the epiphyseal growth plates of the femur or the tibia. Its most common feature is genome disorganization, aneuploidy with chromosomal alterations, deregulation of tumor suppressor genes and of the cell cycle, and an absence of DNA repair. This suggests the involvement of surveillance failures, DNA repair or apoptosis control during osteogenesis, allowing the survival of cells which have undergone alterations during differentiation. Epigenetic events, including DNA methylation, histone modifications, nucleosome remodeling and expression of non-coding RNAs have been identified as possible risk factors for the tumor. It has been reported that p53 target genes or those genes that have their activity modulated by p53, in addition to other tumor suppressor genes, are silenced in OS-derived cell lines by hypermethylation of their promoters. In osteogenesis, osteoblasts are formed from pluripotent mesenchymal cells, with potential for self-renewal, proliferation and differentiation into various cell types. This involves complex signaling pathways and multiple factors. Any disturbance in this process can cause deregulation of the differentiation and proliferation of these cells, leading to the malignant phenotype. Therefore, the origin of OS seems to be multifactorial, involving the deregulation of differentiation of mesenchymal cells and tumor suppressor genes, activation of oncogenes, epigenetic events and the production of cytokines. Contents 1. Introduction 2. Biology of human OS 3. Role of differentiation of mesenchymal stem cells 4. Role of DNA changes 5. Role of deregulating the expression of tumor suppressor genes 6. Regulation of oncogene expression 7. Role of epigenetic mechanisms 8. Role of non-coding RNAs 9. Role of cytokines 10. Conclusion

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“…This abnormal differentiation of pre-osteoblasts resulted in their transformation into osteosarcoma-like cells. Overexpression of sFRP2 affected angiogenesis, a critical phenomenon in cancer invasion and metastasis, and a transcriptomic analysis revealed that sFRP2 overexpression increased the expression of pro-angiogenic and anti-apoptotic genes in endothelial cells [85]. Consistent with these results, Techavichit et al [86] showed the implication of sFRP2 in invasion and metastasis.…”

Section: Using Sfrps In Cancer Therapy?mentioning

confidence: 72%

“…In contrast, Kim et al [85] studied the effect of sFRP2 overexpression in patients with the Li-Fraumeni syndrome, which is characterized by a p53 mutation and an increased incidence of osteosarcoma (500fold higher in comparison with the normal Fig. 9.…”

Section: Using Sfrps In Cancer Therapy?mentioning

confidence: 99%

Secreted Frizzled‐related proteins (sFRPs) in osteo‐articular diseases: much more than simple antagonists of Wnt signaling?

2019

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Osteo‐articular diseases are characterized by a dysregulation of joint and/or bone homeostasis. These include diseases affecting the joints originally, such as osteoarthritis and rheumatoid arthritis, or the bone, such as osteoporosis. Inflammation and the involvement of Wingless‐related integration site (Wnt) signaling pathways are key pathophysiological features of these diseases resulting in tissue degradation by matrix‐degrading enzymes, namely matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTs), secreted by the joint resident cells and/or by infiltrating immune cells. Activation of Wnt signaling pathways is modulated by different families of proteins, including Dickkopfs and the secreted Frizzled‐related proteins (sFRPs). The sFRP family is composed of five secreted glycoproteins in mammals that regulate Wnt signaling in the extracellular compartment. Indeed, sFRPs are able to bind both to the soluble Wnt ligands and to their cell membrane receptors, the Frizzled proteins. Their expression profile is altered in osteo‐articular diseases, suggesting that they could account for the abnormal activation of Wnt pathways. In the present article, we review how sFRPs are more than simple antagonists of the Wnt signaling pathways and discuss their pathophysiological relevance in the context of osteo‐articular diseases. We detail their Wnt‐dependent and their Wnt‐independent roles, with a particular emphasis on their ability to modulate the inflammatory response and extracellular matrix (ECM) remodeling. We also discuss their potential therapeutic use with a focus on bone remodeling, osteo‐articular cancers, and tissue engineering.

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Oncogenic role of sFRP2 in P53-mutant osteosarcoma development via autocrine and paracrine mechanism

Cited by 6 publications

References 95 publications

Modeling Hematological Diseases and Cancer With Patient-Specific Induced Pluripotent Stem Cells

Modeling Hematological Diseases and Cancer With Patient-Specific Induced Pluripotent Stem Cells

Biology and pathogenesis of human osteosarcoma (Review)

Secreted Frizzled‐related proteins (sFRPs) in osteo‐articular diseases: much more than simple antagonists of Wnt signaling?

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