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Ectopic expression of platelet integrin alphaIIb beta3 in tumor cells from various species and histological origin
Abstract:
The integrin alphaIIb beta3 is a membrane receptor which was considered to be expressed only in cells of megakaryocytic lineage. We have shown that alphaIIb beta3 is expressed in mouse melanoma B16a cells, and in human prostate adenocarcinoma cells. The purpose of this study was to determine whether the megakaryocytic product alphaIIb beta3 was functionally expressed in other non-megakaryocyte lineage tumor cells. By using the reverse transcription polymerase chain reaction (RT-PCR), we have obtained data demonstrating that alphaIIb beta3 is expressed in a variety of tumor cell lines (17) derived from different species (human, rat and mouse) and of different histological origins (skin, blood, lung, liver, kidney, cervix, colon, bladder, breast and prostate). Immunostaining of tumor cells with a monoclonal antibody (MAb) to alphaIIb beta3 demonstrates that alphaIIb beta3 protein is also expressed in tumor cells. A protein kinase C activator PMA stimulates adhesion of tumor cells to fibronectin and fibrinogen, and this stimulated adhesion is blocked by a function-blocking MAb directed to alphaIIb beta3. Our results indicate that the megakaryocytic gene product alphaIIb beta3 integrin is widely expressed among tumor cells of non-megakaryocytic lineage, suggesting that ectopic expression of this integrin may play an important role in tumor progression.
Insights
Integrin alphaIIb beta3, typically found in blood cells, is also present in various tumor cells. This ectopic expression suggests a potential role for integrin alphaIIb beta3 in cancer progression.
Area of Science:
- Cell Biology
- Oncology
- Molecular Biology
Background:
- Integrin alphaIIb beta3 is a cell surface receptor traditionally associated with megakaryocytic lineage cells.
- Previous findings indicated its expression was limited to cells of megakaryocytic origin.
- Recent observations have shown alphaIIb beta3 expression in mouse melanoma and human prostate cancer cells.
Purpose of the Study:
- To investigate the functional expression of the megakaryocytic protein, integrin alphaIIb beta3, in diverse non-megakaryocytic tumor cell lines.
- To determine if this integrin plays a role in tumor cell adhesion and progression.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) was employed to detect alphaIIb beta3 gene expression across various tumor cell lines.
- Immunostaining using a monoclonal antibody (MAb) was performed to confirm protein expression.
- Functional assays involved stimulating tumor cell adhesion to fibronectin and fibrinogen with a protein kinase C activator (PMA) and assessing the effect of a function-blocking MAb.
Main Results:
- Integrin alphaIIb beta3 gene expression was detected in 17 different tumor cell lines from humans, rats, and mice, spanning multiple histological origins.
- Immunostaining confirmed the presence of alphaIIb beta3 protein on these tumor cells.
- PMA-stimulated adhesion of tumor cells to fibronectin and fibrinogen was observed, and this adhesion was significantly inhibited by a function-blocking anti-alphaIIb beta3 MAb.
Conclusions:
- The megakaryocytic gene product, integrin alphaIIb beta3, is widely expressed in tumor cells of non-megakaryocytic lineage.
- Ectopic expression of integrin alphaIIb beta3 in these tumor cells suggests a potential role in tumor progression.
- Targeting alphaIIb beta3 may offer a therapeutic strategy for cancers exhibiting its expression.