Advancing Biomedical Science through Tissue Arrays |
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Array-Based Pathology Model
Apoptosis Related Model
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An Example of Pathology-Model Based Target Validation |
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| Background: An in vitro study had suggested that molecule X secreted by tumor cells might induce T cell apoptosis, so as to help tumor cells escape from T cell mediated tumor cell killing. The purpose of the profiling project was to find evidence supporting this suggestion and to evaluate suitability of the molecule as a target for antibody therapeutics. | ||
| Procedures | Results | Picture |
| Antibody production |
 Specific antibody was produced.
The antibody recognized a single band
with correct molecular weight in Western blot (as indicated by
the arrow). |
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| IHC tissue profiling was performed in standard normal tissue arrays. | IHC tissue profiling showed a dominant cytoplasmic staining pattern of the molecule in a wide range of organs of the human body. |
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| IHC tissue profiling was performed in standard tumor tissue arrays. | IHC tissue profiling showed slightly higher than normal expression levels of the molecule in a wide range of tumors. |
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| IHC (left) and TUNEL (right) analyses to correlate apoptic index with expression levels of the molecule in our apoptosis related model. |
       High expression level of the
molecule (left top brown staining indicated by the arrow) did not correlate with the apoptotic index
in the model. The brown dots on the right indicated by arrows
are apoptotic bodies. |
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| IHC detection of CD4 and CD8 populations in the apoptosis model. |
  There were abundant CD4 and CD8
lymphocytes (indicated by arrows) near or within the tumor cells that showed high
level of molecule X. |
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| Pharmacological aspect | IHC showed high expression levels of the molecule in many vital organs. The arrows indicate strong staining in the tubular epithelial cells of the kidney. |
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| Conclusion | Our pathology model-based analyses did not support the original hypothesis that molecule X might induce T cell apoptosis. The high expression levels of the molecule found in many vital organs indicate that the molecule is not suitable as a target for antibody therapeutics. | |
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