Aberrant Expression of Syndecan-1 in Cervical Cancers

Abstract

Syndecan-1, is a transmembrane heparan/chondroitin sulfate proteoglycan necessary for cell-cell and cell-matrix interactions. Its decreased level on the cell surface correlates with poor prognosis in several tumor types. Aberrant stromal localization of syndecan-1 is also considered an unfavorable prognostic factor in various human malignancies. In the presented work the question was addressed if changes in syndecan-1 expression are related to the prognosis of cervical cancer. Immunohistochemistry for syndecan-1 extracellular domain was performed on surgical specimens of primary cervical cancer. To follow the communication between tumor cells and stromal fibroblasts, their mono-and co-cultures were studied, detecting the expression of syndecan-1, smooth muscle actin, vimentin, and desmin. Immunohistochemistry of tumorous specimens revealed that while cell surface syndecan-1 expression was reduced on cancer cells, it appeared on the surface of tumor-associated fibroblasts. Until year 7, the cohort with high cell surface syndecan-1 expression had significantly longer survival. No difference in the same time-period could be detected when stromal syndecan-1 expression was analyzed. In vitro analysis revealed, that tumor cells can induce syndecan-1 expression on fibroblast, and fibroblasts showed that fibroblast-like cells are built by two cell types: (a) syndecan-1 positive, cytokeratin negative real fibroblasts, and (b) syndecan-1 and cytokeratin positive epithelial-mesenchymal transformed tumor cells. Syndecan-1 on the surface of cancer cells appears to be a positive prognostic marker. Although syndecan-1 positive fibroblasts promote tumor cell proliferation in vitro, we failed to detect their cancer promoting effect in vivo.

Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

“…A limitation to our in vitro model is the lack of stromal components, which could significantly influence the behavior of the tumor tissue. Ectopic expression of syndecan-1 in stromal cells has been reported in carcinomas of the cervix [ 95 , 96 ], and stromal syndecan-1 expression was shown to correlate with poor prognosis in some tumor types such as cancers of the stomach [ 97 ], pancreas [ 46 ], endometrium [ 98 ], oral cavity [ 99 ], breast [ 100 , 101 ], bladder [ 48 ], and ovary [ 102 ].…”

Serum syndecan‐4 is associated with nonalcoholic fatty liver disease

“…33 It has been found that soluble SDC1 can be used for noninvasive diagnosis in patients with chronic toxic hepatitis, 34 and it is effective in predicting the prognosis of patients with multiple myeloma, cervical cancer and other malignant tumors. [35][36][37] However, little is known about SDC4 shedding. A previous study found that the genetic deletion of SDC4 altered the body composition, metabolic phenotype and function of metabolic tissues.…”

Differential Impact of Membrane-Bound and Soluble Forms of the Prognostic Marker Syndecan-1 on the Invasiveness, Migration, Apoptosis, and Proliferation of Cervical Cancer Cells

“…Previous studies have indicated a dysregulation of Sdc-1 expression in cervical carcinoma tissues (6,(13)(14)(15)(16)(17). To further investigate the clinicopathological relevance of aberrant Sdc-1 expression in this disease, we made use of large public gene expression datasets.…”

“…Thus, this protein has emerged as a novel target for the development of selective and more potent therapies. Although some studies indicate that Sdc-1 can act both anti-or pro-tumorigenic (13)(14)(15)(16)(17), the mechanisms by which Sdc-1 participates in the pathogenesis and progression of tcervical cancer are still unknown. In this study, we analyzed the dysregulation and prognostic impact of Sdc-1 expression in clinical specimens of cervical cancer utilizing publically available transcriptomic datasets.…”