DC-CLM, a cadherin-like molecule cloned from human dendritic cells, inhibits growth of breast cancer cells.
OBJECTIVE
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.
Jiang
Yingming
Y
Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, 200433, P.R. China.
Wan
Tao
T
Chen
Guoyou
G
Xiu
Fangming
F
Xia
Dajing
D
Zhang
Weiping
W
Zhou
Xiangyang
X
Cao
Xuetao
X
D000595:Amino Acid Sequence; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D015820:Cadherins / Q000235:genetics* / Q000494:pharmacology*; D003001:Cloning, Molecular; D003713:Dendritic Cells; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells; D000091363:Protocadherins; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099152:Cadherin 5
D015703:Antigens, CD; D000970:Antineoplastic Agents; D015820:Cadherins; D000091363:Protocadherins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000099152:Cadherin 5; C473689:PCDHGB6 protein, human; C083970:R-cadherin