elastin and Cell-Transformation--Neoplastic

Topics: Cell Transformation, Neoplastic; Collagen; Cytokines; DNA Mutational Analysis; Elastin; Fibrosis; Humans; Lymphatic Metastasis; Models, Theoretical; Mouth Neoplasms; Mutation; Prognosis; Protein-Lysine 6-Oxidase; Tumor Microenvironment

Topics: Adenocarcinoma, Mucinous; Adipose Tissue; Biomarkers, Tumor; Calmodulin-Binding Proteins; Cell Transformation, Neoplastic; Colorectal Neoplasms; Elastin; Eosine Yellowish-(YS); Hematoxylin; Humans; Mucins; Neoplasm Invasiveness; Neoplasm Staging; Staining and Labeling; Veins

The human fibulin family consists of seven complex extracellular glycoproteins originally characterized as components of elastic fibers in connective tissue. However, beyond its structural role, fibulins are involved in complex biological processes such as cell adhesion, migration or proliferation. Indeed, they have proved to be essential elements in normal physiology, as shown by mouse models lacking these proteins, that evidence several developmental abnormalities and pathological features. Their relevance is also apparent in tumorigenesis, an aspect that has started to be intensely studied. Distinct fibulins are expressed in both tumor and stromal cells and are subjected to multiple expression regulations with either anti or pro-tumor effects. The mechanistic insights that underlie these observations are now commencing to emerge, portraying these proteins as very versatile and active constituents of connective tissue. The aim of this review is to highlight the most relevant connections between fibulins and cancer.

Topics: ADAM Proteins; ADAMTS1 Protein; Animals; Calcium-Binding Proteins; Cell Transformation, Neoplastic; Elastic Tissue; Elastin; Extracellular Matrix; Extracellular Matrix Proteins; Gene Silencing; Humans; Mice; Mice, Knockout; Microfibrils; Neoplasm Proteins; Neoplasms; Oligopeptides; Protein Isoforms

The extracellular matrix (ECM) and a complex interplay of cell-to-cell and cell-to-matrix (ECM) interactions provide important platforms to determine cellular senescence and a potentially tumorigenic transformation of normal human mammary epithelial cells (HMEC). An enhanced formation of extracellular filaments, consisting of elastin-like structures, in senescent post-selection HMEC populations was paralleled by a significantly increased expression of its precursor protein tropoelastin and matched with a markedly elevated activity of the cross-linking enzyme family of lysyl oxidases (LOX). RNAi experiments revealed both the ECM metalloproteinase MMP-7 and the growth factor HB-EGF as potential effectors of an increased tropoelastin expression. Moreover, co-localization of MMP-7 and HB-EGF as well as a concomittant downstream signaling via Fra-1 indicated a possible association between the reduced MMP-7 enzyme activity and an impaired HB-EGF processing, resulting in an enhanced tropoelastin synthesis during senescence of HMEC. In agreement with previous work, these findings suggested an important influence of the extracellular proteinase MMP-7 on the aging process of HMEC, affecting both extracellular remodeling as well as intracellular signaling pathways.

Topics: Cell Transformation, Neoplastic; Cells, Cultured; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p16; Elastin; Epithelial Cells; Female; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Mammary Glands, Human; Matrix Metalloproteinase 7; Middle Aged; Protein-Lysine 6-Oxidase; Proto-Oncogene Proteins c-fos; RNA Interference; Signal Transduction; Time Factors; Tropoelastin

Identify and characterize the matrix metalloproteinase responsible for cartilage proteoglycan degradation mediated by a macrophage cell line in a cell culture model that resembles some aspects of rheumatoid pannus.. Supernatants from the transformed mouse macrophage cell line J774A.1 were used to purify the proteoglycan degrading activity.. J774A.1 macrophage culture supernatants were purified by sequential column chromatography and proteins were identified by zymography, western blotting and amino acid sequence analysis. Cartilage degradation was measured using 35S labeled bovine nasal cartilage.. The cartilage degrading proteolytic activity in the mouse macrophage supernatants proved to be due to two major proteins with approximate molecular masses of 48 kDa and 22 kDa that were identified as macrophage metalloelastase (MME). Incubation of purified MME at 37 degrees C for up to 16 h resulted in the processing of the 48 kDa protein to several novel bands including a previously undescribed protein of approximately 25 kDa without accumulation of fully processed 22 kDa protein. A number of proteinases increased the rate of this processing. J774A.1 macrophage metalloelastase degraded cartilage proteoglycan with an efficiency approximately equal to human macrophage metalloelastase (MMP-12) and matrilysin (MMP-7) and twice that of stromelysin-1 (MMP-3).. These data identify the cartilage proteoglycan degrading metalloproteinase secreted by J774A.1 macrophages in this cell culture model as MME, and describes mechanisms of activation and processing of this enzyme that may play an important role in cartilage degradation.

Topics: Amino Acid Sequence; Animals; Blotting, Western; Cartilage; Cell Line; Cell Transformation, Neoplastic; Connective Tissue; Culture Media, Conditioned; Elastin; Electrophoresis, Polyacrylamide Gel; Macrophages; Matrix Metalloproteinase 12; Metalloendopeptidases; Mice; Molecular Sequence Data; Proteoglycans

A study was done to investigate the presence of type II collagen and elastin in the metaplastic chondroid tissue of 21 pleomorphic adenomas of the major and minor salivary glands. Type II collagen was detected with anti-bovine type II collagen antibody after double digestion of histological sections with trypsin and hyaluronidase. The immunoreaction was positive in the chondrocytic cells and intercellular matrix. Elastic fibers in the chondroid tissue were found by orcein staining; they were scarce and randomly distributed. Although the presence of type II collagen and elastin in the metaplastic chondroid tissue is not directly implicated in the genesis of the tumor, it reveals a unique and high grade of cellular differentiation in comparison with true cartilage.

Topics: Adenoma, Pleomorphic; Adolescent; Adult; Aged; Cartilage; Cell Transformation, Neoplastic; Collagen; Elastin; Female; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Salivary Gland Neoplasms

Topics: Aging; Atrophy; Cell Transformation, Neoplastic; DNA Repair; Elastic Tissue; Elastin; Humans; Mouth Mucosa; Proteoglycans; Skin; Skin Physiological Phenomena

Topics: Aged; Cell Transformation, Neoplastic; Connective Tissue; Elastic Tissue; Elastin; Fibroblasts; Humans; Microscopy, Electron; Middle Aged; Photosensitivity Disorders; Protein Biosynthesis; Proteins; Radiation Effects; Skin Diseases; Skin Neoplasms; Ultraviolet Rays