R V Iozzo

..Thus, decorin should be considered as a novel biological ligand for the EGF receptor, an interaction that could regulate cell growth during remodeling and cancer growth...

....

..The structure-function relationship of some paradigmatic proteoglycans is discussed in depth and novel aspects of their biology are examined...

....

..The binding of one collagen triple helix to decorin is proposed to play a major role in the formation of the staggered arrangement of collagen molecules within the microfibrils by preventing lateral fusion of collagen molecules...

..This study provides the molecular basis for discerning the transcriptional control of the decorin gene and offers the opportunity to investigate genetic disorders linked to this important human gene...

..Using interspecific backcross analysis, we assigned the versican gene (Cspg2) to mouse chromosome 13, in a region that is syntenic with the long arm of human chromosome 5 where the human CSPG2 gene is located...

..These results suggest that bamacan is involved in the control of cell growth and transformation...

..Thus, FGF-BP should be considered a novel biological ligand for perlecan, an interaction that could influence cancer growth and tissue remodeling...

..These results provide the first genetic evidence that the perlecan protein core is a molecular entity implicated in FGF7 binding and activation of its receptor...

..These results will be useful for the study of biglycan gene regulation and for the generation of mice with targeted null mutation of the Bgn gene...

..This study provides the molecular basis for discerning the regulation of the WNT-5A gene and offers the opportunity to investigate genetic disorders linked to this important gene...

..Attenuation of EGFR activity without physical downregulation of the receptor could represent a novel therapeutic approach toward malignancies in which EGFR plays a primary role in tumor growth and survival...

..Additional analyses using panels of human/rodent somatic cell hybrids with specific chromosomal translocations and deletions mapped the human clathrin heavy chain gene locus to 17q11-qter...

..These results provide the first evidence that EGF and decorin converge functionally to regulate the cell cycle through activation of a common pathway which ultimately leads to growth suppression...

..In contrast, the major parenchymal organs were only weakly positive for decorin mRNA. These findings suggest that decorin may play a role in epithelial/mesenchymal interactions during organ development and shaping...

..These results offer insights into the evolution of this chimeric molecule and provide the molecular basis for understanding the transcriptional control of this important gene...

..0002) and in a cohort of intestinal tumors from Apc-deficient Min/+ mice. These results support the concept that deregulated expression of bamacan/SMC3 is involved in cell transformation...

..Thus, perlecan is a potent inducer of tumor growth and angiogenesis in vivo and therapeutic interventions targeting this key modulator of tumor progression may improve cancer treatment...

..Finally, using a combination of Southern blotting, PCR amplification, and in situ hybridization, the human Wnt-5A (WNT5A) gene was mapped to chromosome 3p14-p21...

..Thus, perlecan protein core should be considered a novel biological ligand for FGF7, an interaction that could influence cancer growth and tissue remodeling...

....

..These findings demonstrate a fundamental role for decorin in regulating collagen fiber formation in vivo...

..Collectively, the results indicate that perlecan may play crucial roles not only in vasculogenesis but also in the maturation and maintenance of differentiated tissues, including cartilage...

..Our findings support the hypothesis that MITOSTATIN has many hallmarks of a classical tumor suppressor in solid tumors and may play an important role in cancer development and progression...

..The localization of this proteoglycan locus in the human genome and the availability of new RFLPs provide the tools for future studies of human diseases where the HSPG2 proteoglycan gene is suspected to be involved...

..This study provides the molecular basis for discerning the transcriptional control of the versican gene and offers the opportunity to investigate genetic disorders linked to this important human gene...

..Therefore, in addition to its well-established role in proliferation and differentiation, B-myb also appears to be involved in activation of NK and T cells and in their regulation of Fas/Fas ligand-mediated cytotoxicity..

..Our studies show that this proteoglycan is present in all vascularized tissues and suggest that this unique molecule has evolved from the utilization of modular structures with adhesive and growth regulatory properties...

..Thus, syndecan proteoglycans can directly mediate ligand catabolism through a pathway with characteristics distinct from coated pits, and might act as receptors for atherogenic lipoproteins and other ligands in vivo...

..Furthermore, decorin induced apoptosis via activation of caspase-3. This could represent an additional mechanism whereby decorin might influence cell growth and survival...

..Our findings indicate that decorin is a key regulatory molecule and that the temporal switch from biglycan to decorin is an important event in the coordinate regulation of fibrillogenesis and tendon development...

..Our results suggested a model whereby perlecan regulates these processes via controlling the bioavailability of perlecan-binding soluble factors involved in epidermal morphogenesis...

..In the early phases of the three-dimensional culture, decorin reduced apoptosis. However, following the establishment of a three-dimensional matrix, the cells did not require decorin for their survival...

..New findings indicate a potential functional coupling between the intricate make-up of basement membrane proteoglycans and their ability to control important biological processes...

..Thus, we have discovered a novel biological mechanism for decorin that could explain its anti-proliferative and anti-oncogenic mode of action...

..Variances such as those presented here need to be further characterized and taken into account when designing therapies or replacements for any one particular tendon...

..This might contribute to aneurysmal ventricular dilatation, remote hypertrophy, and depressed ventricular function...

..These findings underscore the importance of the micro-environment in controlling the fate of adult stem cells and reveal a novel cellular and molecular basis for the physiological and pathological control of bone mass...

..This study provides evidence for the involvement of decorin and the IGF-I receptor/mTOR/p70 S6 kinase signaling pathway in the translational regulation of fibrillin-1...

..Therefore, LZTS1 may become an excellent target for gene therapy in advanced bladder carcinoma...

..These two somewhat diametrically opposed roles will be discussed in light of new data emerging from various fields which converge on perlecan as a key regulator of cell growth and angiogenesis...

..We also discuss the role of lumican and LRIG1, a novel cell growth inhibitor homologous to decorin...

..Taken together, our data demonstrate that decorin acts as a tumor suppressor gene and plays an important role in the maintenance of cell maturation and therefore homeostasis in the intestinal tract...

..This review is focused on novel biological functions of SLRPs with special emphasis on their protein cores, newly described genetic diseases, and signaling events in which SLRPs play key functions...

..Thus, biologically active decorin is a monomer in solution and, as such, is a monovalent ligand for various extracellular matrix proteins, growth factors, and cell surface receptors...

..We conclude that decorin is a natural protective factor against diabetic nephropathy and that the Dcn(-/-) diabetic mouse is a useful new model of progressive diabetic nephropathy...

..These results show that lack of Dcn alters the normal interaction between airways and lung parenchyma; in asthma, changes in Dcn could potentially contribute to abnormal airway physiology...

..These data show that at early stages of fibrillogenesis, the glycosaminoglycan chain of decorin has a reducing effect on collagen fibril diameter...

..These results demonstrate a novel role for decorin in reduction or prevention of tumor metastases in this breast cancer model and could eventually lead to improved therapeutics for metastatic breast cancer...

....

..Thus, progranulin/perlecan interaction could contribute to a fine regulation of tumor angiogenesis and could ultimately affect cancer growth...

..Thus capillary morphogenesis requires endothelial alpha2beta1 integrin engagement of a single type I collagen integrin-binding site, possibly signaling via p38 MAPK and focal adhesion disassembly/FAK inactivation...

..Future studies should directly correlate composition and structure with tendon mechanics for the design and evaluation of tissue-engineered constructs or tendon repairs...

..These results provide a novel mechanism of action for decorin, and indicate that decorin could adversely affect in vivo tumor growth by suppressing the endogenous tumor cell production of a powerful angiogenic stimulus...

..Thus, decorin binds to a discrete region of the EGFR, partially overlapping with but distinct from the EGF-binding domain. These findings could lead to the generation of protein mimetics capable of suppressing EGFR function...

..Thus, a physiological interaction could also occur in vivo during development and in pathological events, including tissue remodeling and tumor progression...

..Thus, endorepellin represents a novel anti-angiogenic product, which may retard tumor neovascularization and hence tumor growth in vivo...

..Overall, decorin is shown to be a vital player in maintaining skin and tendon integrity at the molecular level, among other functions...

..This study provides quantitative evidence for structure-function relationships in tendon, including the role of proteoglycan in viscoelasticity...

..CONCLUSION: In the presence of an active AR, the combined production of FGF2 and FGF-BP may play an important role in the progression of prostate cancer through the selection of AR- clones expressing high levels of Bcl-2...

..These results indicate that DCN, in addition to its effects on fibrillogenesis, plays a regulatory role in angiogenesis and that FMOD in endothelial cells may be able to partially substitute for DCN...

..Thus, decorin gene therapy helps in retarding the growth of human tumors in immunocompromised animals and could represent a new independent or adjunctive therapeutic modality against cancer...

..These alterations in lung tissue mechanical behavior in Dcn-/- mice support a critical role for decorin in the formation of the lung collagen network...

..These data suggest that spirochetal DbpA may interact with host decorin during infection and such interactions could be a mechanism that B. burgdorferi uses to evade humoral immunity and establish chronic infection...

..Therefore, in a large multivariate model, GAG content was the largest predictor of mechanical properties, perhaps both through direct influence and indirectly through its correlation with collagen content and fibril structure...

..Our results indicate a novel role for decorin and biglycan during pressure-induced renal injury by stimulating fibrillin-1 expression...

....

....

..These data demonstrate that caspase-3 activation is a novel pathway of importance for triggering extracellular CathL release and the cleavage of extracellular matrix components...

..These findings indicate that perlecan is essential for the integrity of somitic muscle and developmental angiogenesis and that endorepellin mediates most of these biological activities...

..These results suggest that decorin-mediated tissue organization is strongly dependent upon tissue type and mechanical environment...

..By more fully understanding perlecan's functioning in angiogenesis, we may gain invaluable insight that could lead to therapeutic interventions in cancer and other pathologic states...

..In contrast, AG879 failed to have any effect. Our data support a role for decorin as a powerful and effective therapeutic agent against breast cancer due to its inhibition of both primary tumor growth and metastatic spreading...

..We conclude that the angiostatic effects of endorepellin in vivo are mediated by a specific interaction of endorepellin with the alpha2beta1 integrin receptor...

..These data indicate that decorin is an important player in the IGF system and its loss cannot fully be compensated in different types of diseases...

..In this review we will discuss modern proteomic strategies that may improve the laboratory assessment of PROM, and will focus on some of the biochemical characteristics of agrin and perlecan fragments identified in amniotic fluid...

....

..In the long term, additional SFK members are recruited for sustaining the anti-apoptotic response, which could play crucial roles in abnormal fibrogenic healing...

..CONCLUSIONS: Our results provide support for the hypothesis that endorepellin is an effective antitumor vasculature agent that could be used as a therapeutic modality to combat cancer...

..These studies also suggest a heretofore unrecognized role for angiostatic basement membrane fragments in platelet biology...

....

....