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Changes in integrin receptors on oncogenically transformed cells
1Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Abstract:
Oncogenically transformed cells show reduced assembly of fibronectin-rich extracellular matrixes and diminished ability to adhere to fibronectin. The molecular bases of these phenotypic alteration are not fully understood. We report here alterations in the spectrum of integrins, including two fibronectin receptors, on oncogenic transformation of rodent cells. Transformation of rat1, NRK, and Nil8 cells by Rous sarcoma virus or by murine sarcoma viruses encoding ras oncogenes leads to reductions in the level of integrin alpha 5 beta 1, which is a well-defined fibronectin receptor, and of two other integrin receptors. In contrast, another receptor, alpha 3 beta 1, which is a polyspecific receptor for fibronectin, laminin, and collagen, is retained by transformed cells. These results provide explanations for earlier results concerning the interactions of extracellular matrix proteins with the surfaces of tumor cells and offer leads to further understanding of the altered adhesive and migratory behavior of malignant cells.
Insights
Oncogenic transformation reduces key fibronectin receptors (integrin alpha 5 beta 1) on cells, impacting their adhesion. This explains altered tumor cell behavior and extracellular matrix interactions.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Oncogenic transformation alters cell behavior, including extracellular matrix (ECM) interactions.
- Reduced fibronectin matrix assembly and cell adhesion are observed in transformed cells.
- The underlying molecular mechanisms for these changes remain unclear.
Purpose of the Study:
- To investigate alterations in integrin expression during oncogenic transformation.
- To identify specific fibronectin receptors affected by oncogenic transformation.
- To elucidate the molecular basis for diminished cell adhesion in cancer cells.
Main Methods:
- Utilized rodent cell lines (rat1, NRK, Nil8) for transformation studies.
- Employed Rous sarcoma virus and ras oncogenes for cellular transformation.
- Analyzed changes in integrin receptor expression using biochemical and molecular techniques.
Main Results:
- Oncogenic transformation led to decreased levels of integrin alpha 5 beta 1, a primary fibronectin receptor.
- Expression of two additional integrin receptors was also reduced post-transformation.
- Integrin alpha 3 beta 1, a polyspecific receptor, remained expressed in transformed cells.
Conclusions:
- Alterations in integrin expression, particularly the reduction of alpha 5 beta 1, explain reduced fibronectin adhesion in transformed cells.
- These findings provide molecular insights into the altered adhesive and migratory properties of malignant cells.
- The study offers a basis for understanding tumor cell interactions with the extracellular matrix.
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