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Functional cloning of ARM-1, an adhesion-regulating molecule upregulated in metastatic tumor cells
A B Simins1, H Weighardt, K M Weidner
1Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität, München, Germany.
Abstract:
Interactions of tumor cells with the endothelium and tissue stroma are considered to be critical steps in metastasis formation and progression of cancer. To identify cellular receptors that mediate the binding of tumor cells to endothelium, a murine T cell lymphoma-derived expression library was screened for adhesion-inducing cDNA clones. We identified a novel cell adhesion-promoting molecule, termed ARM-1 (adhesion regulating molecule-1), which is homologous to a human Mr 110,000 tumor-associated antigen. The ARM-1 cDNA codes for a type I transmembrane protein of 407 amino acids with potential O- and N-glycosylation sites that does not belong to any of the known families of cell adhesion molecules. Overexpression of ARM-1 in 293T human embryonic kidney cells significantly increased adhesion to different endothelial cells. ARM-1 expression in 293T cells did not alter integrin expression or beta1-integrin-mediated cell adhesion. Northern blot analysis of human breast cancer cell lines revealed 3- to 5-fold elevated ARM-1 mRNA levels in metastatic as compared to non-metastatic cells. In conclusion, we have identified ARM-1 as a novel cell adhesion-promoting receptor that is upregulated in metastatic cancer cells.
Insights
Researchers identified a novel cell adhesion molecule, adhesion regulating molecule-1 (ARM-1), crucial for cancer cell metastasis. ARM-1 is upregulated in metastatic cells, promoting tumor cell adhesion to endothelium.
Area of Science:
- Molecular biology
- Cell biology
- Oncology
Background:
- Tumor cell interactions with endothelium and stroma are critical for metastasis.
- Identifying cellular receptors mediating tumor cell-endothelium binding is key to understanding cancer progression.
Purpose of the Study:
- To identify novel cellular receptors involved in tumor cell adhesion to endothelium.
- To characterize a newly discovered adhesion molecule, ARM-1, and its role in cancer metastasis.
Main Methods:
- Screening a murine T cell lymphoma expression library for adhesion-inducing cDNA clones.
- Identifying and characterizing the ARM-1 gene and protein.
- Overexpressing ARM-1 in 293T cells and assessing adhesion to endothelial cells.
- Analyzing ARM-1 mRNA levels in human breast cancer cell lines via Northern blot.
Main Results:
- A novel cell adhesion-promoting molecule, ARM-1, was identified.
- ARM-1 is a type I transmembrane protein, 407 amino acids long, with no known cell adhesion molecule homology.
- ARM-1 overexpression significantly increased tumor cell adhesion to endothelial cells.
- Elevated ARM-1 mRNA levels (3- to 5-fold) were observed in metastatic versus non-metastatic breast cancer cells.
Conclusions:
- ARM-1 is a novel cell adhesion receptor.
- ARM-1 plays a significant role in promoting tumor cell adhesion.
- ARM-1 is upregulated in metastatic cancer cells, suggesting its involvement in metastasis.