Abstract
Purpose
To identify the characteristics and function of a cadherin-like molecule, cloned from a human dendritic cell (DC) cDNA library and designated DC-derived cadherin-like molecule (DC-CLM).
Methods
The mRNA expression of DC-CLM in tissues and cells was analyzed by Northern blot and RT-PCR, respectively. In order to express DC-CLM in target cells, we constructed a pcDNA3.1/DC-CLM expression vector and transfected it into MCF-7 human breast cancer cells. Tumor growth was demonstrated by cell proliferation and colony formation.
Results
DC-CLM cDNA encoded a protein of 260 amino acids and the gene was localized to chromosome 5q31. The predicted protein possessed a definitive cadherin-specific sequence motif and shared homology with classical cadherin. However, no transmembrane segment was observed in DC-CLM. Northern blot revealed the ubiquitous nature of DC-CLM transcripts in human tissues, with high expression in heart, brain, prostate, testis and ovary. RT-PCR demonstrated that DC-CLM was widely expressed in hematopoietic and epithelial tumor cell lines, but was not expressed in MCF-7. Interestingly, DC-CLM expression was upregulated in DC activated by lipopolysaccharides. DC-CLM expression in the stable transfectant (MCF-7/DC-CLM) was confirmed by RT-PCR and Western blot. DC-CLM protein was found to be secreted by MCF-7/DC-CLM but not expressed on the membrane of MCF-7/DC-CLM. DC-CLM transfection resulted in significant inhibition of in vitro growth and colony formation of MCF-7 cells.
Conclusions
A cadherin-like molecule DC-CLM was cloned from human DC and it may be a soluble cadherin-like molecule for tumor suppression. DC-CLM was upregulated in activated DC and may be involved in the effector function of activated DC.
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Acknowledgements
We sincerely thank Mrs. Mei Jin and Mrs. Qunying Shi for their excellent technical assistance.
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This work was supported by grants from the National Natural Science Foundation (30100166, 30121002) and the National Key Basic Research Program of China (2001CB510002)
Y.J. and T.W. contributed equally to this work.
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Jiang, Y., Wan, T., Chen, G. et al. DC-CLM, a cadherin-like molecule cloned from human dendritic cells, inhibits growth of breast cancer cells. J Cancer Res Clin Oncol 129, 57–64 (2003). https://doi.org/10.1007/s00432-002-0404-8
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DOI: https://doi.org/10.1007/s00432-002-0404-8