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/
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.
It is composed of the following phtyochemicals: (1)
Bacopa monniera extract (45% bacosides), 150 mg; (2)
Silybum marianum extract (70%–80% silymarin), 225 mg; (3)
Withania somnifera (Indian ginseng) powder, 150 mg; (4) green tea extract (
Camellia sinensis, 98% polyphenols and 45% epigallocatechin-3 gallate), 75 mg; and (5) curcumin (95%) from
Curcuma longa, 75 mg. Individual ingredients of Protandim
® are well-known antioxidants that cause induction of SOD and catalase in rodents and diminish cellular lipid peroxidation.
mg/Kg and induced diabetic nephropathy. After a 8weeks, EGCG groups (n=7/each group) were received EGCG 50
