Browsing by Subject "Proteoglycan"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Publication
    Open Access
    Development, differentiation, and vascular components of subcutaneous and intrahepatic Hepa129 tumors in a mouse model of hepatocellular carcinoma
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Robertson, Richard T.; Gutierrez, Paula M.; Baratta, Janie L.; Thordarson, Kristoffer; Braslow, Joshua; Haynes, Sherry M.; Longmuir, Kenneth J.
    Tumor models in mice offer opportunities for understanding tumor formation and development of therapeutic treatments for hepatocellular carcinoma. In this study, subcutaneous or intra-hepatic Hepa129 tumors were established in C3H mice. Tumor growth was determined by daily measurements of subcutaneous tumors and post-mortem studies of subcutaneous and intrahepatic tumors. Administration of Edu was used to determine cell generation dates of tumor cells. Immunohistochemistry with antibodies directed at CD31 or CD34, and intravenous injection of labeled tomato lectin revealed tumor vasculature. Tissue sections also were processed for immunohistochemistry using a panel of antibodies to proteoglycans. Comparison of Edu labeled cells with immunoreactivity allowed determination of development and differentiation of tumor cells after cell generation. Subcutaneous and intrahepatic tumors displayed similar growth over 3 weeks. Immunohistochemistry showed strong labeling for glypican-3, 9BA12, and chondroitin sulfate of tumors in both loci, while normal liver was negative. Tumor regions containing Edu labeled cells did not show significant immunohistochemical labeling for the tumor markers until 2-3 days after Edu treatment; overlap of Edu labeled cells and immunohistochemically labeled tumor regions appeared to reach a maximum at 5 days after Edu treatment. Ectopic subcutaneous tumors displayed vascular ingrowth as the tumor cells expressed immunocytochemical markers; subcutaneous tumors displayed significantly more vascular elements than did intrahepatic tumors.
  • Thumbnail Image
    Publication
    Open Access
    Heparanase and heparanase 2 display differently deregulation in neuroendocrine tumors, depending on their differentiation grade
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) García, Beatriz; García-Suárez, Olivia; Fernández-Vega, Iván; Vallina, Aitana; Astudillo, Aurora; Quirós, Luis M.
    Heparanase is a glucuronidase that appears upregulated in many human cancers and is involved in cellular invasion and tumor metastasis. Heparanase 2 is a homologue of heparanase that lacks enzymatic activity and displays anti-metastatic features. The aim of this work was to analyze the expression of both molecules in neuroendocrine tumors. We investigated the transcription of heparanases in lung neuroendocrine tumors well- and poorly differentiated using RT-PCR, and the expresion of the proteins by means of immunohistochemistry. The tumors were selected according to different malignancy WHO 2013 grades and were arranged in tissue arrays. The prometastatic enzyme heparanase appeared overexpressed in well- but not in poorly differentiated tumors, irrespective of their location. Moreover, the anti-metastatic heparanase 2 increased its expression in well-differentiated tumors, but strongly decreased in poorly differentiated ones, again independently of anatomic origin. Given the involvement of both molecules in tumor progression, through both their catalytic and non-enzymatic properties, there would seem to be a relationship between the regulation of their expression and the features of the neuroendocrine tumor.
  • Thumbnail Image
    Publication
    Open Access
    Immunohistochemical evaluation of versican, in relation to chondroitin sulphate, in canine mammary tumours
    (Murcia : F. Hernández, 2003) Erdélyi, I.; Nieskens, D.H.M.; van Dijk, J.E.; Vass, L.; Nederbragt, H.
    The expression of increased amounts of versican, a chondroitin sulphate proteoglycan, in neoplastic tissues may play a role in promoting tumour cell proliferation and migration. This study investigated the immunolocalization of versican in normal and neoplastic canine mammary tissues, using antibodies 12C5 and 2B1, against different epitopes of the protein core of versican. Antibody CS56, recognising chondroitin sulphate (CS), was used to investigate the relation between versican and CS, which accumulates in canine mammary tumours. We found enhanced versican expression in both benign and malignant tumours, appearing in three main patterns: in periductal tissues, probably in association with basement membranes of ducts; in peripheral invasive areas of malignant tumours; and in spindle cell proliferations and myxoid areas of complex and mixed tumours. The 12C5 and 2B1 immunoreactivities co-localised in all types of tumours, and could be improved by chondroitinase digestion. The only exception was the abundant extracellular matrix (ECM) of spindle cell proliferations, particularly in myxoid areas of complex and mixed tumours, which displayed intense and diffuse 12C5 immunoreactivity and patchy or absent 2B1 and CS56 immunoreactivities; versican immunoreactivity could not be enhanced by chondroitinase digestion. The results indicate that versican is one of the extracellular matrix components characteristic of canine mammary tumours. It appears likely that in complex and mixed tumours versican exists in at least two forms, one of them lacking the CS attachment domain and the 2B1 epitope. Furthermore, the enhanced versican expression in the invasive areas of malignant tumours indicates the involvement of this proteoglycan in tumour cell invasion.
  • Thumbnail Image
    Publication
    Open Access
    New aspects of the pathogenesis of osteoarthritis: the role of fibroblast-like chondrocytes in late stages of the disease
    (Murcia : F. Hernández, 2005) Tesche, F.; Miosge, Nicolai
    It is thought that the general increase in life expectancy will make osteoarthritis the fourth leading cause of disability by the year 2020. Even though the pathogenesis of idiopathic osteoarthritis has not been fully elucidated, the main features of the disease process are the altered interactions between the chondrocytes and their surrounding extracellular matrix. In the course of these disturbances, three types of chondrocytes are typically present in the pathologically altered extracellular matrix of the articular cartilage: healthy chondrocytes which are continually undergoing degeneration, degenerated cells which are continually being degraded and finally fibroblast-like chondrocytes which seem not to be influenced by this process and, therefore, are found in ever-increasing numbers. These fibroblast-like chondrocytes take part in tissue regeneration even in advanced stages of osteoarthritis, but only in as much as they form fibrocartilaginous or scar tissue, since, as we were able to show, they mainly synthesize collagen type I and not collagen type II, typical for healthy cartilage. However, we were further able to show that fibroblast-like chondrocytes also produce increasing amounts of the proteoglycans decorin and biglycan which physiologically are involved in the formation of collagen type II, as well as perlecan. These multifunctional fibroblast-like chondrocytes could present an ideal therapeutic starting point if they could be modified to synthesize the collagen type II typical for cartilage and to, thereby, contribute to reversing the damage of the joint cartilage that has occurred by the late stages of osteoarthritis.
  • Thumbnail Image
    Publication
    Open Access
    Quantitative detection of anionic sites in rat femoral velscartilage using cationic colloidal gold at low pH le
    (Murcia : F. Hernández, 1998) Ueda, H.; Kato, Y.; Ohno, S.
    Quantitative analyses of anionic sites in the rat cartilage were performed by using post-embedding LR-Gold method with cationic colloidal gold (CCG) at different pH levels. Alteration of the pH levels affected the CCG staining patterns. The CCG particles were more observed at low pH levels, 1.0 and 2.5, than those at high pH 7.4. So, we quantitatively examined the superficial, intermediate and deep layers at pH 1.0. Morphometric analyses showed that CCG particles were increased from the superficial layer to the deep layer in both pericellular matrix (PM) and interterritorial matrix (IM). Moreover, they were more observed in PM than in IM. After chondroitinase ABC digestion, the CCG labeling was reduced in all matrices of the superficial and intermediate layers, though many CCG particles were still observed in PM of the deep layer. After hyaluronidase digestion, the CCG labeling was markedly reduced in the PM of the deep layer. These findings suggest that anionic sites in the cartilage matrix are detected by using the CCG only at low pH levels. In addition, the PM in the deep layer may consist of different components from those of the other two layers.