Aberrant Expression of Syndecan-1 in Cervical Cancers
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ORIGINAL ARTICLE
Aberrant Expression of Syndecan-1 in Cervical Cancers Katalin Karászi 1 & Renáta Vigh 1 & Miklós Máthé 1 Zoltán Papp 2,3 & Ilona Kovalszky 1
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Alexandra Fullár 1
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Lászlóné Oláh 1
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Tibor Füle 1
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Received: 21 April 2020 / Accepted: 28 April 2020 # The Author(s) 2020
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 syndecan1 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 syndecan1 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. Keywords Syndecan-1 . Cervical cancer . Survival analysis . Cancer-associated fibroblasts . Extracellular matrix remodeling
Introduction In spite of recent advances in prevention, early diagnosis, effective screening and treatment programs, cervical cancer is still associated with the fourth highest mortality rate in women oncology worldwide [1, 2].
Stromal cells and extracellular matrix (ECM) elements have tremendous impact on the nature of cancer. The tumor cells remodel their local surrounding environment by the production of stimulatory factors and cytokines forming the tumorous neostroma which contains cancer-associated fibroblasts (CAFs), endothelial cells and inflammatory cells [3].
* Ilona Kovalszky [email protected]; [email protected]
Tibor Füle [email protected] Zoltán Papp [email protected]
Katalin Karászi [email protected] Renáta Vigh [email protected]
1
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üll
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