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Published on: June 3, 2016
Syndecan-1 regulates adipogenesis: new insights in dedifferentiated liposarcoma tumorigenesis
Laure-Emmanuelle Zaragosi1, Bérengère Dadone2, Jean-François Michiels3
1Institute of Biology Valrose, UMR7277 CNRS/UMR1091 INSERM/University of Nice-Sophia Antipolis, 06108 Nice, France, Present address: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, University of Nice- Sophia Antipolis, 06560 Sophia Antipolis, France.
Abstract:
Syndecan-1 (SDC1/CD138) is one of the main cell surface proteoglycans and is involved in crucial biological processes. Only a few studies have analyzed the role of SDC1 in mesenchymal tumor pathogenesis. In particular, its involvement in adipose tissue tumors has never been investigated. Dedifferentiated liposarcoma, one of the most frequent types of malignant adipose tumors, has a high potential of recurrence and metastastic evolution. Classical chemotherapy is inefficient in metastatic dedifferentiated liposarcoma and novel biological markers are needed for improving its treatment. In this study, we have analyzed the expression of SDC1 in well-differentiated/dedifferentiated liposarcomas and showed that SDC1 is highly overexpressed in dedifferentiated liposarcoma compared with normal adipose tissue and lipomas. Silencing of SDC1 in liposarcoma cells impaired cell viability and proliferation. Using the human multipotent adipose-derived stem cell model of human adipogenesis, we showed that SDC1 promotes proliferation of undifferentiated adipocyte progenitors and inhibits their adipogenic differentiation. Altogether, our results support the hypothesis that SDC1 might be involved in liposarcomagenesis. It might play a prominent role in the dedifferentiation process occurring when well-differentiated liposarcoma progress to dedifferentiated liposarcoma. Targeting SDC1 in these tumors might provide a novel therapeutic strategy.
Insights
Syndecan-1 (SDC1) is overexpressed in dedifferentiated liposarcoma, promoting tumor cell proliferation and inhibiting differentiation. Targeting SDC1 may offer a new therapeutic strategy for this aggressive cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Syndecan-1 (SDC1/CD138), a cell surface proteoglycan, plays roles in various biological processes.
- Limited research exists on SDC1's role in mesenchymal tumors, particularly adipose tissue tumors.
- Dedifferentiated liposarcoma is an aggressive adipose tumor with high recurrence and metastatic potential, lacking effective chemotherapy.
Purpose of the Study:
- To investigate the expression and role of SDC1 in liposarcoma pathogenesis.
- To determine if SDC1 is involved in the dedifferentiation process of liposarcoma.
- To explore SDC1 as a potential therapeutic target for liposarcoma.
Main Methods:
- Analysis of SDC1 expression in well-differentiated/dedifferentiated liposarcomas and normal adipose tissue.
- Silencing SDC1 in liposarcoma cells to assess effects on viability and proliferation.
- Utilizing a human adipogenesis model to study SDC1's impact on adipocyte progenitors.
Main Results:
- SDC1 is significantly overexpressed in dedifferentiated liposarcoma compared to normal adipose tissue and lipomas.
- Silencing SDC1 reduced liposarcoma cell viability and proliferation.
- SDC1 enhanced proliferation of undifferentiated adipocyte progenitors and hindered their adipogenic differentiation.
Conclusions:
- SDC1 is implicated in liposarcomagenesis and may drive the dedifferentiation process in liposarcoma.
- SDC1 overexpression is a hallmark of dedifferentiated liposarcoma.
- Targeting SDC1 presents a potential novel therapeutic strategy for liposarcoma treatment.
