Institute 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.
Department of Pathology, Nice University Hospital, 06202 Nice, France, Institute for Research on Cancer and Aging of Nice, CNRS UMR 7284/INSERM U1081, University of Nice-Sophia Antipolis, 06107 Nice, France, Laboratory of Solid Tumor Genetics, Nice University Hospital, 06107 Nice, France and.
Carcinogenesis. 2015 Jan;36(1):32-40. doi: 10.1093/carcin/bgu222. Epub 2014 Oct 24.
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.
硫酸乙酰肝素蛋白聚糖 1（SDC1/CD138）是主要的细胞表面蛋白聚糖之一，参与许多重要的生物学过程。仅有少数研究分析了 SDC1 在间叶组织肿瘤发病机制中的作用。特别是，其在脂肪组织肿瘤中的作用从未被研究过。去分化脂肪肉瘤是最常见的恶性脂肪肿瘤之一，具有很高的复发和转移进化潜能。经典的化疗在转移性去分化脂肪肉瘤中无效，需要新的生物标志物来改善其治疗效果。在这项研究中，我们分析了 SDC1 在高分化/去分化脂肪肉瘤中的表达情况，结果表明，与正常脂肪组织和脂肪瘤相比，SDC1 在去分化脂肪肉瘤中高度过表达。在脂肪肉瘤细胞中沉默 SDC1 会损害细胞活力和增殖。使用人类多能脂肪源性干细胞的人类脂肪生成模型，我们发现 SDC1 促进未分化脂肪细胞祖细胞的增殖，并抑制其脂肪生成分化。总之，我们的结果支持 SDC1 可能参与脂肪肉瘤发生的假说。它可能在从高分化脂肪肉瘤进展为去分化脂肪肉瘤时发生的去分化过程中发挥重要作用。在这些肿瘤中靶向 SDC1 可能提供一种新的治疗策略。
