Oral squamous carcinoma cells secrete RANKL directly supporting osteolytic bone loss

Objective: Local invasion of bone is a frequent complication of oral squamous cell carcinoma (OSCC). Development of these osteolytic lesions is mediated by osteoclasts. Receptor activation of NF-kappa B ligand (RANKL) signaling, counteracted by osteoprotegerin (OPG), regulates osteoclastogenesis. Previous studies in rodent models have demonstrated that inhibition of RANKL decreases tumor growth and lesions within bone. However, the contributory role of OSCC cells to this disease process has yet to be defined.Methods: RANKL expression was assessed in a panel of OSCC cell lines by qPCR, flow cytometry, and ELISA. Induction of osteoclastogenesis was assessed by co-culture with macrophages or with OSCC-derived conditioned medium. In an animal model of bone invasion, nude mice were injected intratibially with UMSCC-11B cells expressing a RANKL luciferase promoter to detect tumor-derived RANKL activity. Osteolytic lesions were analyzed by X-ray, micro-CT, and histological methods. RANKL expression was assessed in human OSCC tissues by immunohistochemistry.Results: We demonstrated that OSCCs express varied levels of all RANKL isoforms, both membrane-bound and soluble RANKL. Both co-culture and treatment with OSCC-conditioned media induced osteoclastogenesis. In mice, we demonstrated human RANKL promoter activity during bone invasion. Over the course of the experiment, animals suffered osteolytic lesions as RANKL-driven luciferase expression increased with time. After 8 weeks, human-derived RANKL was detected in areas of bone resorption by immunohistochemistry. Similar epithelial RANKL expression was detected in human OSCC tissues.Conclusion: These data demonstrate the ability of OSCCs to produce RANKL, directly altering the tumor microenvironment to increase osteoclastogenesis and mediate local bone invasion. (C) 2012 Elsevier Ltd. All rights reserved.

Morphological changes and parasite load of the adrenal from dogs with visceral leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Direct laser writing by two-photon polymerization as a tool for developing microenvironments for evaluation of bacterial growth

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Investigation of Human Albumin-Induced Circular Dichroism in Dansylglycine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Perfil gênico no oviduto bovino de fêmeas Nelore e Aberdeen angus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Immunoexpression of S100A4 in canine skin melanomas and correlation with histopathological parameters

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Proteins, Pathogens, and Failure at the Composite-Tooth Interface

In the United States, composites accounted for nearly 70% of the 173.2 million composite and amalgam restorations placed in 2006 (Kingman et al., 2012), and it is likely that the use of composite will continue to increase as dentists phase out dental amalgam. This trend is not, however, without consequences. The failure rate of composite restorations is double that of amalgam (Ferracane, 2013). Composite restorations accumulate more biofilm, experience more secondary decay, and require more frequent replacement. In vivo biodegradation of the adhesive bond at the composite-tooth interface is a major contributor to the cascade of events leading to restoration failure. Binding by proteins, particularly gp340, from the salivary pellicle leads to biofilm attachment, which accelerates degradation of the interfacial bond and demineralization of the tooth by recruiting the pioneer bacterium Streptococcus mutans to the surface. Bacterial production of lactic acid lowers the pH of the oral microenvironment, erodes hydroxyapatite in enamel and dentin, and promotes hydrolysis of the adhesive. Secreted esterases further hydrolyze the adhesive polymer, exposing the soft underlying collagenous dentinal matrix and allowing further infiltration by the pathogenic biofilm. Manifold approaches are being pursued to increase the longevity of composite dental restorations based on the major contributing factors responsible for degradation. The key material and biological components and the interactions involved in the destructive processes, including recent advances in understanding the structural and molecular basis of biofilm recruitment, are described in this review. Innovative strategies to mitigate these pathogenic effects and slow deterioration are discussed.

HPV16-associated tumors control myeloid cell homeostasis in lymphoid organs, generating a suppressor environment for T cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fabrication of microenvironments with different geometrical features for cell growth studies

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

O local de nidificação do sabiá-barranco (Turdus Leucomelas) (Aves, Turdidae) afeta a temperatura interna do ninho durante a incubação e cuidado à prole?

Individuals of the species Turdus leucomelas are adapted to live in environments already modified by humans, thus obtaining reproductive success in their nesting in vegetation, as well as built their nests in human buildings. Nests found in buildings are often less camouflaged, making them more exposed to predators compared to nests built in vegetation; however the nests built buildings are common, indicating a possible advantage associated with these nests. By means of this idea if was assumed that a possible advantage to this construction in buildings is linked to a change in variation in the internal temperature of the nest during incubation and development of pups until they leave their nests. Accordingly, with the aid of iButtons and TidBits (temperature data loggers), the present study aimed to analyze the influence of the nesting site on how the temperature is kept, and how it changes in the microenvironment in which the nest is inserted, indicating potential benefits associated with that choice. In the samples found with the vegetation, temperature data showed a pattern of temperature of the microenvironment of the nests is not very stable, varying with ambient temperature, whereas in the samples found with the human constructions, the temperature data showed a pattern of temperature microenvironment nests more stable for a long time. When comparing the two environments which they settled nests, as well as the different times of day (daytime and nighttime), how the temperature was kept and pattern of change within the nest was significantly different (F=43.85, p<0.001), with higher and more constant internal temperatures in nests installed in construction, compared to vegetation. When observing periods of the day, it was found that in both environments the temperature inside the nest reached higher values and higher than the environment at night, coinciding with the rest of the female at night. Data may suggest changes in the...

Avaliação do uso de Selante de Fibrina derivado do veneno de serpente como arcabouço biológico de células tronco mesenquimais na regeneração óssea do fêmur de ratos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Interação de fibroblastos associados ao câncer em co-cultura com linguagens tumorias mamárias e a resposta terapêutica em o uso da melatonina

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

MicroRNAs targeting the immunomodulatory HLA-G gene: a new survey searching for microRNAs with potential to regulate HLA-G

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Androgen therapy reverses injuries caused by ethanol consumption in the prostate: testosterone as a possible target to ethanol-related disorders

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)