ABSTRACT
Extracellular matrix (ECM) proteins in the mammary gland provide structure and regulate its development and homeostasis. Alterations in its structure can regulate and support pathogenesis, like breast tumors. Aiming to identify the health and tumoral canine mammary ECM scaffold protein profile by immunohistochemistry, the decellularization process was carried out to remove the cellular content. Additionally, it was verified the influence of health and tumoral ECM on the attachment of health and tumoral cells. The types I, III, IV, and V structural collagens were scarce in the mammary tumor, and ECM fibers were disorganized. Vimentin and CD44 were more common in mammary tumor stroma, suggesting a role in cell migration that results in tumor progression. Elastin, fibronectin, laminin, vitronectin, and osteopontin were similarly detected under healthy and tumor conditions, providing the attachment of normal cells in healthy ECM, while tumoral cells were able to attach in tumoral ECM. The protein pattern demonstrates ECM alteration in canine mammary tumorigenesis, presenting new knowledge on mammary tumor ECM microenvironment.
Subject(s)
Extracellular Matrix Proteins , Neoplasms , Animals , Dogs , Extracellular Matrix Proteins/metabolism , Extracellular Matrix/metabolism , Laminin , Connective Tissue , Neoplasms/pathology , Tumor MicroenvironmentABSTRACT
Galectin-8 (Gal-8) is a tandem-repeat type galectin with affinity for ß-galactosides, bearing two carbohydrate recognition domains (CRD) connected by a linker peptide. The N- and C-terminal domains (Gal-8N and Gal-8C) share 35% homology, and their glycan ligand specificity is notably dissimilar: while Gal-8N shows strong affinity for α(2-3)-sialylated oligosaccharides, Gal-8C has higher affinity for non-sialylated oligosaccharides, including poly-N-acetyllactosamine and/ or A and B blood group structures. Particularly relevant for understanding the biological role of this lectin, full-length Gal-8 can bind cell surface glycoconjugates with broader affinity than the isolated Gal-8N and Gal-8C domains, a trait also described for other tandem-repeat galectins. Herein, we aim to discuss the potential use of separate CRDs in modelling tandem-repeat galectin-8 and its biological functions. For this purpose, we will cover several aspects of the structure-function relationship of this protein including crystallographic structures, glycan specificity, cell function and biological roles, with the ultimate goal of understanding the potential role of each CRD in predicting full-length Gal-8 involvement in relevant biological processes.
Subject(s)
Carbohydrate Metabolism , Galectins/metabolism , Amino Acid Sequence , Crystallography, X-Ray , Galectins/chemistry , Humans , Ligands , Protein Conformation , Sequence Homology, Amino AcidABSTRACT
Os mecanismos biológicos desenvolvidos para aumentar a qualidade da regeneração óssea e da reparação tecidual de sítios periodontais específicos continuam a ser um desafio e têm sido complementado pela capacidade de adesão celular do colágeno do tipo I, promovida por um peptídeo sintético de adesão celular (P-15), associado a uma matriz inorgânica de osso (MIO) para formar MIO/P-15. O objetivo deste estudo foi avaliar a perda do nível clínico de inserção e a resposta da bolsa periodontal em dentes após 3 e 6 meses da aplicação de enxerto com MIO/P-15. Vinte e um cães do Hospital Veterinário da Universidade de São Paulo foram anestesiados para realização de tratamento periodontal e 132 faces dentais com perda de nível clínico de inserção foram tratadas, sendo que 36,4 por cento (48 faces) receberam o peptídeo de adesão celular e 63,6 por cento (84 faces) compuseram o grupo controle que recebeu tratamento convencional (retalho muco-gengival e aplainamento radicular). O procedimento foi documentado através de radiografia intra-oral e todas as sondagens de bolsas periodontais foram fotografadas. Depois de 3 e de 6 meses, os animais foram re-anestesiados a fim de se obter novas avaliações, radiografias, fotografias e sondagens periodontais. As 48 faces com perda de nível clínico de inserção que receberam material de enxertia apresentaram taxa de 40 por cento de recuperação do nível clínico de inserção após 6 meses. O grupo controle de faces dentais não apresentou alteração do nível clínico de inserção. A face palatina foi a que apresentou melhor taxa de regeneração (40 por cento) e os dentes caninos e molares mostraram as melhores respostas (57,14 por cento e 65 por cento, respectivamente). Não houve sinais de infecção pós-cirúrgica relacionadas à falta de higienização oral dos animais. Pode-se concluir que o MIO/P-15 auxilia na regeneração e re-aderência das estruturas periodontais, incluindo osso alveolar. Sua aplicação mostrou-se fácil...
The development of biologic modalities designed to enhance bone regeneration and wound healing of specific periodontal sites continues to be a challenge and has been accomplished through the cell binding activity of Type-I collagen. These have been provided by a synthetic cell biding peptide (P-15), associated to a anorganic bone matrix (ABM) to form ABM/P-15. The aim of this study was to evaluate the attachment loss and periodontal pocket response in teeth after 3 and 6 months with ABM/P-15 graft application. Twenty one dogs from the Veterinary Hospital, University of São Paulo, were anesthetized in order to accomplish periodontal treatment and 132 teeth faces with attachment loss were treated. From these, 36.4 percent (48 faces) received cell binding peptide and 63.6 percent (84 faces) compounded the control group that received conventional treatment (muco-gingival flap and root planning). The procedure was documented by intra-oral radiography and all periodontal probings were photographed. After 3 and 6 months, the animals were re-anesthetized in order to accomplish new photography, radiography and periodontal probing exams. The 48 attachment loss faces that received graft material exhibited 40 percent of regeneration rate after 6 months. The control faces did not change their attachment level. The palatal face presented the better regeneration rates (40 percent) and the canines and molars teeth showed the better responses (57.14 percent and 65 percent, respectively). There was no post-surgical infection related to absence of oral home care. It can be concluded that ABM/P-15 helps a more rapidly periodontal structure re-attachment and regeneration, including alveolar bone. Its application was easy and practical, and the post-surgical complications incidence was low. Nevertheless, more work is necessary to evaluate the amount and the quality of formed bone and periodontal ligament.