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Molecular mechanisms of cell adhesion in normal and transformed cells
Abstract:
Alterations in the adhesive mechanisms of cancer cells are likely to play an important role in determining the invasive or metastatic potential of these cells. An understanding of these alterations at the molecular level is now within reach, due to recent progress in the identification and characterization of several cell adhesion molecules (CAMs). Two of these molecules, the neural cell adhesion molecule N-CAM and the liver cell adhesion molecule L-CAM, are expressed on a variety of cell types from early embryos and throughout adult life, and appear to play several important roles in early inductive events, formation of specific intercellular connections, and maintenance of adult tissues. Two other molecules, the neuron-glia adhesion molecule Ng-CAM and a molecule involved in the specific adhesion of lymphocytes, appear to be more restricted in their developmental expression and function. The molecular characterization of N-CAM made possible for the first time an examination of the effects of transformation on the expression of a defined cell adhesion molecule. In both established cell lines from rat cerebellum and embryonic chick neuroepithelial cells, transformation by Rous sarcoma virus caused a large reduction in expression of N-CAM. In both cases, the N-CAM-mediated adhesion was correspondingly reduced. The neuroepithelial cells also became more highly motile after transformation. The decrease in N-CAM coupled with this increase in cell motility may significantly enhance the invasiveness of these cells. Other surface antigens have also been identified that may be involved in essential steps of invasion and metastasis. Such studies represent the initial step toward a detailed understanding of the role of CAMs in the various steps of metastasis. The accessibility of CAMs on tumor cell surfaces, and the availability of specific antibodies to these components suggests that reagents may become available in the near future that will offer new opportunities for preventing the formation of metastases.
Insights
Cancer cell adhesion molecule (CAM) alterations impact metastasis. Rous sarcoma virus transformation reduced neural cell adhesion molecule (N-CAM) expression, increasing cell motility and potentially invasiveness, offering insights into metastasis prevention.
Area of Science:
- Molecular biology
- Cell biology
- Cancer research
Background:
- Alterations in cancer cell adhesion mechanisms are crucial for invasion and metastasis.
- Cell adhesion molecules (CAMs) are key to understanding these changes at a molecular level.
- N-CAM and L-CAM are widely expressed CAMs involved in development and tissue maintenance, while Ng-CAM and lymphocyte adhesion molecules have more restricted roles.
Purpose of the Study:
- To investigate the effects of viral transformation on the expression of neural cell adhesion molecule (N-CAM).
- To determine the relationship between N-CAM expression, cell adhesion, and motility in transformed cells.
- To explore the potential role of CAMs in cancer invasion and metastasis.
Main Methods:
- Molecular characterization of N-CAM expression in transformed cell lines.
- Assessing N-CAM-mediated adhesion in control and transformed cells.
- Measuring cell motility in response to transformation.
Main Results:
- Rous sarcoma virus transformation significantly reduced N-CAM expression in rat cerebellum and embryonic chick neuroepithelial cells.
- N-CAM-mediated cell adhesion was correspondingly decreased following transformation.
- Transformed neuroepithelial cells exhibited increased motility.
Conclusions:
- Reduced N-CAM expression and increased motility following transformation may enhance cancer cell invasiveness.
- CAMs are implicated in the essential steps of cancer invasion and metastasis.
- Targeting CAMs on tumor cells may offer future strategies for preventing metastasis.