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  • 1.
    Bendrik, Christina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Karlsson, Lisa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Increased endostatin generation and decreased angiogenesis via MMP-9 by tamoxifen in hormone dependent ovarian cancer2010Inngår i: CANCER LETTERS, ISSN 0304-3835, Vol. 292, nr 1, s. 32-40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There are several similarities between breast and ovarian cancer but anti-estrogen treatment is rarely used in ovarian cancer. We have previously shown that the most widely used anti-estrogen tamoxifen increased MMP-9 activity and endostatin generation in breast cancer. Here, we show that tamoxifen exposure of highly hormone responsive ovarian cancer cells decreased proliferation, and increased MMP-9 activity leading to increased levels of endostatin both in cell culture in vitro and in solid tumors of nude mice. Tamoxifen exposed tumors also exhibited significantly decreased tumor growth and vascularisation. Moreover, in ascites from ovarian cancer patients, MMP-9 was undetectable in majority of cases but a significant correlation of MMP-2 and endostatin was found. The effects on MMPs and endostatin generation are previously unknown mechanisms of estradiol and tamoxifen in ovarian cancer, which may have therapeutic implications in future anti-cancer options of hormone dependent ovarian cancer.

  • 2.
    Karlsson, Lisa K.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Junker, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Grenegård, Magnus
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Kratz, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Brännskadevård. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Human Dermal Fibroblasts and Single-Cell Clone Fibroblasts Have theCapacity to Alter Their Phenotype Towardsan Endothelial-Like Cell type2009Inngår i: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    We investigated the capacity of normal human dermal fibroblasts to alter their phenotype into an endothelialcell-like phenotype. By utilising in vitro cell culture models, the part played by different types of serum andmedium constituents in inducing a phenotypic change of fibroblasts was investigated. The experiments usedprimary cultures of human endothelial cells, human dermal fibroblasts and single-cell clone fibroblasts. Thelatter cell type was obtained by clonal expansion using a micromanipulator technique. The results showed thatthe presence of human serum in the cell culture medium caused both types of fibroblasts to express vonWillebrand factor, to incorporate fluorochrome-labelled LDL, and to start forming capillary-like networks in asimilar way to endothelial cells. The phenotypic shift was detectable after 4 days of cell culture and reached amaximum after 7-10 days. To our knowledge this is the first report to describe differentiation of humanfibroblasts towards an endothelial cell-like phenotype. The results also show that the underlying mechanism ofthe phenotypic shift is a change in gene expression in the dermal fibroblasts and not fusion between different celltypes. Collectively, the present results indicate that human dermal fibroblasts may be a novel cell source forcreating vascular endothelium.

  • 3.
    Karlsson, Lisa K
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Junker, Johan P E
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Grenegård, Magnus
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Kratz, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Human Dermal Fibroblasts: A Potential Cell Source for Endothelialization of Vascular Grafts2009Inngår i: Annals of Vascular Surgery, ISSN 0890-5096, E-ISSN 1615-5947, Vol. 23, nr 5, s. 663-674Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Recently, there has been an intense ongoing search for suitable cell sources for vascular tissue engineering. Previous studies report that cells with multilineage potential have been found within the connective stroma of the skin. In line with this, preliminary data from our group suggest that human dermal fibroblasts have the capacity to alter their phenotype into an endothelial cell-like phenotype in vitro. As a first step in using these cells in vascular tissue engineering, we investigated their ability to form an endothelial cell-like layer on a scaffold in vitro. Furthermore, we studied the possibility of seeding dermal fibroblasts on a scaffold and later commencing with induction toward an endothelial cell-like phenotype. METHODS: Cells cultured in either normal fibroblast medium or endothelial induction medium were seeded on a gelatin-based scaffold. To study the organization of cells, routine staining was performed. Differentiation was confirmed by Western blotting and immunohistochemistry with antibodies directed toward molecules commonly used to identify endothelial cells. RESULTS AND CONCLUSION: Our data support that human dermal fibroblasts differentiated toward endothelial cell-like cells prior to seeding showed histological resemblance to mature endothelial cells, while fibroblasts seeded and later induced into endothelial differentiation grew in multilayer. However, expression of various surface molecules indicative of an endothelial phenotype was seen using both techniques. In conclusion, the results presented in this study indicate that human dermal fibroblasts differentiated toward an endothelial cell-like phenotype may be a novel cell source for endothelialization of vascular grafts.

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