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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Exp+Mol+Pathol
2014 ; 97
(2
): 259-65
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Systemic distribution, subcellular localization and differential expression of
sphingosine-1-phosphate receptors in benign and malignant human tissues
#MMPMID25084322
Wang C
; Mao J
; Redfield S
; Mo Y
; Lage JM
; Zhou X
Exp Mol Pathol
2014[Oct]; 97
(2
): 259-65
PMID25084322
show ga
AIMS: Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4
and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and
progression of various cancers. However, none of the S1PRs have been systemically
investigated. In this study, we performed immunohistochemistry (IHC) for
S1PR1-S1PR5 on different tissues, in order to simultaneously determine the
systemic distribution, subcellular localization and expression level of all five
S1PRs. METHODS: We constructed tissue microarrays (TMAs) from 384 formalin-fixed
paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues
from 34 human organs/systems. Then we performed IHC for all five S1PRs
simultaneously on these TMA slides. The distribution, subcellular localization
and expression of each S1PR were determined for each tissue. The data in benign
and malignant tissues from the same organ/tissue were then compared using the
Student's t-test. In order to reconfirm the subcellular localization of each S1PR
as determined by IHC, immunocytochemistry (ICC) was performed on several
malignant cell lines. RESULTS: We found that all five S1PRs are widely
distributed in multiple human organs/systems. All S1PRs are expressed in both the
cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the
nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes.
Each S1PR is unique in its organ distribution, subcellular localization and
expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has
the highest expression level (in either the nucleus or cytoplasm), with S1PR1, 3,
2 and 4 following in descending order. Strong nuclear expression was seen for
S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four
organs/tissues (adrenal gland, liver, brain and colon) show significant
differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic),
nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft
tissues and uterus) show differences for only one S1PR (cytoplasmic or nuclear),
and twenty three organs/tissues show no significant difference in IHC scores for
any S1PR (cytoplasmic or nuclear) between benign and malignant changes.
CONCLUSION: This is the first study to evaluate the expression level of all S1PRs
in benign and malignant tissues from multiple human organs. This study provides
data regarding the systemic distribution, subcellular localization and
differences in expression of all five S1PRs in benign and malignant changes for
each organ/tissue.