Colon cancer cells expressing cell surface GRP78 as a marker for reduced tumorigenicity
| Autor: | Alexander Vilkin, Maxim Yakimov, Britta Hardy, Yaron Niv, Annat Raiter |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Cell type Pathology medicine.medical_specialty Colorectal cancer Population Cell Mice Downregulation and upregulation Biomarkers Tumor medicine Animals Humans Gene Silencing education Endoplasmic Reticulum Chaperone BiP Heat-Shock Proteins Tumor Stem Cell Assay Cell Proliferation Mice Inbred BALB C education.field_of_study biology Immunomagnetic Separation Cell growth Cell Membrane Liver Neoplasms General Medicine HCT116 Cells medicine.disease Gene Expression Regulation Neoplastic Cell Transformation Neoplastic medicine.anatomical_structure Oncology Colonic Neoplasms Cancer research biology.protein Molecular Medicine Antibody |
| Zdroj: | Cellular Oncology. 35:345-354 |
| ISSN: | 2211-3436 2211-3428 |
| DOI: | 10.1007/s13402-012-0094-4 |
| Popis: | The glucose regulated heat shock protein 78 (GRP78) is a central regulator of ER (endoplasmic reticulum) stress due to its pro-survival property. Up regulated GRP78 expression in tumor cells has been correlated with aggressive malignancies whereas some reports have predicted an improved prognosis. Over-expression of GRP78 in the ER promotes its localization to the cell surface on several cell types including tumor cells. In order to elucidate whether GRP78 receptor positive and negative tumor cells manifest different properties in colorectal cancer, we first artificially separated GRP78 positive and negative sub-populations from HM7 and HCT116 cell lines using anti GRP78 antibody coated magnetic beads. Only GRP78 negative cells were highly proliferative, induced significant growth in tumor size in nude mice and metastasized to the liver in a human metastatic colorectal carcinoma model in mice. In contrast, GRP78 positive cells manifested reduced proliferation, colony formation, tumor growth and liver metastases. The reduced tumorigenicity of GRP78 positive subpopulation was abrogated by silencing GRP78 expression using siRNA oligomers. In our efforts to induce cell surface GRP78, we subjected the cells to doxorubicin and taxol that increased significantly the percent of GRP78 positive population. Cells pre-incubated with doxorubicin exhibited reduced proliferation and tumor growth in mice. This study demonstrates the significance of cell surface GRP78 in colon cancer, which may be used as a marker for reduced tumorigenicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|