scholarly journals Acid-Induced Inflammatory Cytokines in Osteoblasts: A Guided Path to Osteolysis in Bone Metastasis

Author(s):  
Gemma Di Pompo ◽  
Costantino Errani ◽  
Robert Gillies ◽  
Laura Mercatali ◽  
Toni Ibrahim ◽  
...  

Bone metastasis (BM) is a dismal complication of cancer that frequently occurs in patients with advanced carcinomas and that often manifests as an osteolytic lesion. In bone, tumor cells promote an imbalance in bone remodeling via the release of growth factors that, directly or indirectly, stimulate osteoclast resorption activity. However, carcinoma cells are also characterized by an altered metabolism responsible for a decrease of extracellular pH, which, in turn, directly intensifies osteoclast bone erosion. Here, we speculated that tumor-derived acidosis causes the osteoblast–osteoclast uncoupling in BM by modulating the pro-osteoclastogenic phenotype of osteoblasts. According to our results, a low pH recruits osteoclast precursors and promotes their differentiation through the secretome of acid-stressed osteoblasts that includes pro-osteoclastogenic factors and inflammatory mediators, such as RANKL, M-CSF, TNF, IL-6, and, above the others, IL-8. The treatment with the anti-IL-6R antibody tocilizumab or with an anti-IL-8 antibody reverted this effect. Finally, in a series of BM patients, circulating levels of the osteolytic marker TRACP5b significantly correlated with IL-8. Our findings brought out that tumor-derived acidosis promotes excessive osteolysis at least in part by inducing an inflammatory phenotype in osteoblasts, and these results strengthen the use of anti-IL-6 or anti-IL-8 strategies to treat osteolysis in BM.

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Giulio Maccauro ◽  
Maria Silvia Spinelli ◽  
Sigismondo Mauro ◽  
Carlo Perisano ◽  
Calogero Graci ◽  
...  

The metastasis is the spread of cancer from one part of the body to another. Two-thirds of patients with cancer will develop bone metastasis. Breast, prostate and lung cancer are responsible for more than 80% of cases of metastatic bone disease. The spine is the most common site of bone metastasis. A spinal metastasis may cause pain, instability and neurological injuries. The diffusion through Batson venous system is the principal process of spinal metastasis, but the dissemination is possible also through arterial and lymphatic system or by contiguity. Once cancer cells have invaded the bone, they produce growth factors that stimulate osteoblastic or osteolytic activity resulting in bone remodeling with release of other growth factors that lead to a vicious cycle of bone destruction and growth of local tumour.


PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0207404
Author(s):  
Gokul Raj Kathamuthu ◽  
Kadar Moideen ◽  
Vaithilingam V. Banurekha ◽  
Dina Nair ◽  
R. Sridhar ◽  
...  

1979 ◽  
Vol 83 (1) ◽  
pp. 260-265 ◽  
Author(s):  
M Chinkers ◽  
J A McKanna ◽  
S Cohen

The morphological effects of epidermal growth factor (EGF) on human carcinoma cells A-431 have been examined by scanning electron microscopy. These flat polygonal cells normally exhibit only small membrane folds, but show extensive ruffling and extension of filopodia within 5 min of exposure to EGF at 37 degrees C. This ruffling activity is transient, subsiding within another 5--15 min, but several other changes in surface morphology follow. Within the first hour of exposure to the hormone, the cell surface becomes exceedingly smooth and the nuclei seem to protrude above the plane of the otherwise thin monolayer, giving the cells a "fried egg" appearance. Cells at the edges of colonies gradually retract from the substrate, leading to reorganization, by 12 h, of the monolayer into multilayered colonies. EGF thus induces both rapid and long-term alterations in the morphology of these epidermoid cells.


1992 ◽  
Vol 126 (4) ◽  
pp. 315-318 ◽  
Author(s):  
L Upadhyaya ◽  
JK Agrawal ◽  
GP Dubey ◽  
KN Udupa

Circulating levels of T3, T4, γ-amino-butyric acid, glutamate, 5-hydroxytryptamine, histamine, monoamine oxidase and histaminase were studied in 45 (2 5M, 20F) hyperthyroid patients and 46 (2 5M, 21F) normal healthy volunteers. Increased levels of blood 5-hydroxytryptamine, histamine and glutamic acid were observed along with elevated T3 and T4, whereas plasma γ-aminobutyric acid, monoamine oxidase and histaminase activities were found to be low in both male and female patients. After three months of treatment, circulating levels of 5-hydroxytryptamine, histamine and glutamic acid decreased significantly along with normalization of thyroid hormones and with an increase in the concentrations of γ-aminobutyric acid, monoamine oxidase and histaminase. There was a positive correlation between these amines and thyroid hormone levels. The findings thus suggest that alterations in the metabolism of biogenic amines may be related to an altered metabolism in thyrotoxicosis, and these parameters may prove to be useful markers for diagnosis and follow-up of these patients.


2007 ◽  
Vol 1 (6) ◽  
pp. 534-540
Author(s):  
V. V. Bagaeva ◽  
K. A. Avrov ◽  
G. F. Reshetnikova

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