Current diagnostics and treatment of fibrosarcoma -perspectives for future therapeutic targets and strategies

Augsburger, Daniela; Nelson, Peter J.; Kalinski, Thomas; Udelnow, Andrej; Knösel, Thomas; Hofstetter, Monika; Qin, Ji Wei; Wang, Yan; Gupta, Arvid Sen; Bonifatius, Susanne; Li, Minglun; Bruns, Christiane; Zhao, Yue

doi:10.18632/oncotarget.20136

Cited by 106 publications

(101 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Such patients undergo chemotherapy with palliative intent . The most important way to improve prognosis in fibrosarcoma patients is to prevent tumor invasion and metastasis . To examine the possible contribution of GSK3β to invasive tumor growth, the invasive capacity of sarcoma and fibroblast cells was monitored and scored using the collagen gel invasion assay.…”

Section: Resultsmentioning

confidence: 99%

“…Studies have shown only limited survival benefit from adjuvant chemotherapy for high‐risk patients with metastatic or residual disease, although synovial sarcoma is relatively chemosensitive compared to other STS . Adult‐type fibrosarcoma is a rare and highly aggressive subtype of STS, with most patients aged between 30 and 60 years . Fibrosarcoma is characterized by low sensitivity to radio‐ and chemotherapy and by a high rate of tumor recurrence.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glycogen synthase kinase 3β as a potential therapeutic target in synovial sarcoma and fibrosarcoma

et al. 2019

View full text Add to dashboard Cite

derived growth factor; pGSK3β S9 , GSK3β phosphorylated in S9 residue; pGSK3β Y216 , GSK3β phosphorylated in Y216 residue; RTK(s), receptor-type tyrosine kinase(s) AbstractSoft tissue sarcomas (STSs) are a rare cancer type. Almost half are unresponsive to multi-pronged treatment and might therefore benefit from biologically targeted therapy. An emerging target is glycogen synthase kinase (GSK)3β, which is implicated in various diseases including cancer. Here, we investigated the expression, activity and putative pathological role of GSK3β in synovial sarcoma and fibrosarcoma, comprising the majority of STS that are encountered in orthopedics. Expression of the active form of GSK3β (tyrosine 216-phosphorylated) was higher in synovial sarcoma (SYO-1, HS-SY-II, SW982) and in fibrosarcoma (HT1080) tumor cell lines than in untransformed fibroblast (NHDF) cells that are assumed to be the normal mesenchymal counterpart cells. Inhibition of GSK3β activity by pharmacological agents (AR-A014418, SB-216763) or of its expression by RNA interference suppressed the proliferation of sarcoma cells and their invasion of collagen gel, as well as inducing their apoptosis.These effects were associated with G0/G1-phase cell cycle arrest and decreased expression of cyclin D1, cyclin-dependent kinase (CDK)4 and matrix metalloproteinase 2. Intraperitoneal injection of the GSK3β inhibitors attenuated the growth of SYO-1 and HT1080 xenografts in athymic mice without obvious detrimental effects. It also mitigated cell proliferation and induced apoptosis in the tumors of mice. This study indicates that increased activity of GSK3β in synovial sarcoma and fibrosarcoma sustains tumor proliferation and invasion through the cyclin D1/CDK4-mediated pathway and enhanced extracellular matrix degradation. Our results provide a biological basis for GSK3β as a new and promising therapeutic target for these STS types. K E Y W O R D Scell cycle, glycogen synthase kinase 3β, invasion, migration, soft tissue sarcoma

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glycogen synthase kinase 3β as a potential therapeutic target in synovial sarcoma and fibrosarcoma

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Adult type fibrosarcoma (FS) is a malignant tumor thought to arise from fibroblasts and is characterized histologically by undifferentiated spindle cells ( 76 ). Only a few studies point to the existence of CSCs within FSs.…”

Section: Evidence For Cscs In Soft-tissue Sarcomasmentioning

confidence: 99%

Soft Tissue Sarcoma Cancer Stem Cells: An Overview

et al. 2018

View full text Add to dashboard Cite

Soft tissue sarcomas (STSs) are an uncommon group of solid tumors that can arise throughout the human lifespan. Despite their commonality as non-bony cancers that develop from mesenchymal cell precursors, they are heterogeneous in their genetic profiles, histology, and clinical features. This has made it difficult to identify a single target or therapy specific to STSs. And while there is no one cell of origin ascribed to all STSs, the cancer stem cell (CSC) principle—that a subpopulation of tumor cells possesses stem cell-like properties underlying tumor initiation, therapeutic resistance, disease recurrence, and metastasis—predicts that ultimately it should be possible to identify a feature common to all STSs that could function as a therapeutic Achilles' heel. Here we review the published evidence for CSCs in each of the most common STSs, then focus on the methods used to study CSCs, the developmental signaling pathways usurped by CSCs, and the epigenetic alterations critical for CSC identity that may be useful for further study of STS biology. We conclude with discussion of some challenges to the field and future directions.

show abstract

“…Fibrosarcoma is one of the highly amalgamating malignant tumors of mesenchymal tissue origin, among over 50 histological subtypes of soft tissue sarcoma (STS) . This cancer primarily originates in deep soft tissues, tendons, and bones, and has an alarming metastatic potential that poses a significant health concern . Most of the clinicopathological factors proposed for its prognosis and diagnosis are not reliable due to heterogeneity in its underlying biology and atypical symptoms .…”

Section: Introductionmentioning

confidence: 99%

miR‐197‐5p inhibits sarcomagenesis and induces cellular senescence via repression of KIAA0101

Jain

Roy

Das

et al. 2019

Molecular Carcinogenesis

View full text Add to dashboard Cite

The abnormal expressions of microRNAs (miRNAs) are known to be associated with various pathophysiological processes that lead to the development of a plethora of diseases including cancer. Among several miRNAs studied so far, miR-197 has been reported to play a vital role either as an oncogene or tumor suppressor in different cancers. However, its role in carcinogenesis of fibrosarcoma has not yet been elucidated. Therefore, the current study investigated the role of miR-197-5p, which is significantly downregulated in HT1080 fibrosarcoma cells compared to IMR90-tert fibroblast cells. The transient overexpression of miR-197-5p causes a significant decrease in viability and proliferation of fibrosarcoma cells in both concentration-and time-dependent manners. Interestingly, we did not observe any significant changes in cell cycle pattern or apoptotic cell populations, but rather noticed cellular senescence of fibrosarcoma cells upon overexpression of miR-197-5p. Further, this miRNA suppresses the metastatic properties, such as migration, invasion, and anchorageindependent growth of fibrosarcoma possibly through targeting KIAA0101, which is a proliferating cell nuclear antigen-associated factor and overexpressed in the malignancy. In nutshell, our result revealed that miR-197-5p acts as an oncosuppressor miRNA in fibrosarcoma through target regulation of KIAA0101, which can be exploited for developing RNA-based therapeutic strategies for the cure of this malignancy.

show abstract

Current diagnostics and treatment of fibrosarcoma -perspectives for future therapeutic targets and strategies

Cited by 106 publications

References 97 publications

Glycogen synthase kinase 3β as a potential therapeutic target in synovial sarcoma and fibrosarcoma

Glycogen synthase kinase 3β as a potential therapeutic target in synovial sarcoma and fibrosarcoma

Soft Tissue Sarcoma Cancer Stem Cells: An Overview

miR‐197‐5p inhibits sarcomagenesis and induces cellular senescence via repression of KIAA0101

Contact Info

Product

Resources

About