My understanding is the expression of SPP1 is regulated epigenetically in GISTs, and high expression of SPP1 is a novel and independent prognostic parameter in GISTs.
Epigenetic regulation of Secreted Phosphoprotein 1 (SPP1) expression was analysed at mRNA and protein levels in GIST882 and GIST48b cells after treatment with a demethylating agent. Impacts on tumorigenesis-related signalling pathways were analysed by Western Blot after stimulation of GIST cell lines with SPP1.
Conclusion
The expression of SPP1 is regulated epigenetically in GISTs, and high expression of SPP1 is a novel and independent prognostic parameter in GISTs.
http://c953383.r83.cf2.rackcdn.com/file_attachment/attachments/8876/originalcfd8084a371c346654a98fd5c586daaf.html?1330573778
http://www.wikigenes.org/e/gene/e/6696.html
RELATION WITH MERCURY? Unknown.
BREAST CANCER LINK.
Moreover, Spp1 expression correlates with disease prognosis for numerous cancers including breast cancer where it is associated with disease progression and metastasis.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665764/
. http://en.wikipedia.org/wiki/Osteopontin#Potential_clinical_application "The fact that OPN interacts with multiple cell surface receptors which are ubiquitously expressed makes it an active player in many physiological and pathological processes including wound healing, bone turnover, tumorigenesis, inflammation, ischemia and immune responses1. Therefore, manipulation of plasma OPN levels may be useful in the treatment of autoimmune diseases, cancer metastasis, osteoporosis and some forms of stress.[2]"
Ssecreted phosphoprotein 1 (SPP1) OR Osteopontin (OPN), also known as bone sialoprotein I (BSP-1 or BNSP), early T-lymphocyte activation (ETA-1), secreted phosphoprotein 1 (SPP1), 2ar and Rickettsia resistance (Ric), is a human gene product,[1] which is also conserved in other species. Osteopontin is a SIBLING glycoprotein that was first identified in 1986 in osteoblasts.
Potential clinical application
The fact that OPN interacts with multiple cell surface receptors which are ubiquitously expressed makes it an active player in many physiological and pathological processes including wound healing, bone turnover, tumorigenesis, inflammation, ischemia and immune responses1. Therefore, manipulation of plasma OPN levels may be useful in the treatment of autoimmune diseases, cancer metastasis, osteoporosis and some forms of stress.[2]Role in autoimmune diseases
OPN has been implicated in pathogenesis of rheumatoid arthritis. For instance, researchers found that OPN-R, the thrombin-cleaved form of OPN, was elevated in the rheumatoid arthritis joint. However, the role of OPN in rheumatoid arthritis is still unclear. One group found that OPN knock-out mice were protected against arthritis.[47] while others were not able to reproduce this observation.[48] OPN has been found to play a role in other autoimmune diseases including autoimmune hepatitis, allergic airway disease, and multiple sclerosis.[49]Role in cancers and inflammatory diseases
It has been shown that OPN drives IL-17 production;[50] OPN is overexpressed in a variety of cancers, including lung cancer, breast cancer, colorectal cancer, stomach cancer, ovarian cancer, papillary thyroid carcinoma, melanoma and pleural mesothelioma; OPN contributes both glomerulonephritis and tubulointerstitial nephritis; and OPN is found in atheromatous plaques within arteries. Thus, manipulation of plasma OPN levels may be useful in the treatment of autoimmune diseases, cancer metastasis, osteoporosis and some forms of stress.[2]Research has implicated osteopontin in excessive scar-forming and a gel has been developed to inhibit its effect.[51]
Role in allergy and asthma
Osteopontin has recently been associated with allergic inflammation and asthma. Using a murine model of allergic inflammation, it was demonstrated that OPN-s, the secreted form of OPN, exerts opposing effects on mouse Th2 effector responses and subsequent allergic airway disease: pro-inflammatory at primary systemic sensitization, and anti-inflammatory during secondary pulmonary antigenic challenge, mainly through the regulation of different dendritic cell subsets.[52] OPN deficiency was also reported to protect against remodeling and bronchial hyperresponsiveness (BHR), again using a chronic allergen-challenge model of airway remodeling.[53] Furthermore, it was recently demonstrated that OPN expression is upregulated in human asthma, is associated with remodeling changes and its subepithelial expression correlates to disease severity.[54] OPN has also been reported to be increased in the sputum supernatant of smoking asthmatics,[55] as well as the BALF and bronchial tissue of smoking controls and asthmatics.[56]Role in muscle disease and injury
Evidence is accumulating that suggests that osteopontin plays a number of roles in diseases of skeletal muscle, such as Duchenne muscular dystrophy. Osteopontin has been described as a component of the inflammatory environment of dystrophic and injured muscles,[22][57][58][59] and has also been shown to increase scarring of diaphragm muscles of aged dystrophic mice.[60] A recent study has identified osteopontin as a determinant of disease severity in patients with Duchenne muscular dystrophy.[61] This study found that a mutation in the osteopontin gene promoter, known to cause low levels of osteopontin expression, is associated with a decrease in age to loss of ambulation and muscle strength in patients with Duchenne muscular dystrophy.MANIPULATION OF OSTEOPONTIN/SPP1
The Dietary Supplement Protandim® Decreases Plasma Osteopontin and Improves Markers of Oxidative Stress in Muscular Dystrophy Mdx Mice
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2926985/
The nutritional supplement Protandim® has been shown to reduce plasma TBARS by approximately 40% in healthy human subjects after 4 months of treatment, with significant inductions of the antioxidant enzymes superoxide dismutase and catalase
Our data demonstrate a remarkably similar finding in mdx mice with a reduction in plasma TBARS of approximately 48% after 6 months of treatment. Our plasma TBARS result suggests that induction of antioxidant enzymes by a combination of phytochemicals reduces oxidative stress in mdx mice.
- which is nearly equivalent to the manufacturers recommended human dose of 675 mg per day for a 60 kg adult, or 422 mg/m2.
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Abstract
Osteopontin (OPN) is a secreted, integrin-binding matrix phosphorylated glycoprotein that is overexpressed in many advanced cancers. However, the functional mechanisms by which OPN contributes to gastric cancer development are poorly understood. Here, we report that curcumin inhibited the growth of SGC7901 cell and induced apoptosis in a concentration- and time-dependent manner, while the acquired expression of OPN in SGC7901 cells dramatically promoted cell survival under serum depletion and prevented curcumin-induced apoptosis. Furthermore, PI3-K inhibitor LY294002 attenuated OPN-mediated Akt activation. Moreover, inhibiting the binding of OPN to αvβ3 integrins reduced activation of Akt. Taken together, these results demonstrate that the pro-survival and anti-apoptosis activities of OPN in gastric cancer cells are mediated in part through PI3-K/Akt pathway via αvβ3 integrins.
Therapeutic effects of epigallocatechin gallate on streptozotocin-induced diabetic nephropathy in mice.
http://www.krcp-ksn.com/article/S2211-9132%2812%2900472-X/abstract
Diabetic nephropathy is one of the most serious complications in diabetes mellitus and has been the most common cause of end-stage renal disease. Green tea extracts have antioxidant properties, and (-)-epigallocatechin 3-O-gallate (EGCG) is known to be the most abundant in green tea. Osteopontin (OPN) is a large phosphoglycoprotein adhesion molecule, and has emerged as a potentially key pathophysiologic contributor in diabetic nephropathy. We examined whether EGCG could amelliorate the development of diabetic nephropathy and its role of OPN. The mice (n=28) were divided into 3 groups. Control group (n=7) was intraperitoneal (IP) injected 0.9% saline, Streptozotocin (STZ) group (n=7) was IP injected STZ 200
mg/Kg and induced diabetic nephropathy. After a 8weeks, EGCG groups (n=7/each group) were received EGCG 50mg/kg and 100mg/kg
body weight by subcutaneous injection. Serum glucose, blood urea
nitrogen, serum creatinine, urine volume and urine protein amounts were
measured. Western blot assay of OPN was compared for the different
groups. Histopathologic examination and immunohistochemical staining of
mice kidney were performed. Compared with control group, STZ-group
showed an increase in blood glucose, blood urea nitrogen, creatinine
levels and urine protein amounts, and a decrease in body weight. All the
above parameters were significantly reversed with EGCG treatment. After
STZ injection, there were an diabetic glomerulosclerosis with increased
renal OPN accumulation and its protein expression in the kidney cortex.
EGCG-treated mice kidney showed a reduced expression of above
parameters and an reserved pathologic findings. These results suggest
that EGCG ameliorates STZ-induced diabetic nephropathy by OPN
suppression. The potential use of EGCG in the treatment of diabetic
nephropathy should be further explored.
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