The expression pattern of E- and
P-cadherin in human
carcinomas has been reported by many laboratories. However, little is known about the involvement of other
cadherin types in human
carcinomas.
cDNA clones for a
cadherin molecule were isolated from a cDNA library of human
hepatocellular carcinoma cells which lacked E- and
P-cadherin expression but exhibited cell aggregation activity mediated by an unknown
cadherin, and they were subjected to sequence analysis. The overlapped clones covered 4315
nucleotides and were found to encode a typical
cadherin molecule consisting of 790
amino acids. Since the deduced amino acid sequence was identical to a partially available human
cadherin-6 sequence except for two
amino acid residues, the clones were considered to be human
cadherin-6 cDNAs encoding the entire open reading frame. The deduced amino acid sequence also showed extremely high homology with recently reported rat
K-cadherin, 97% for the putative mature
protein, suggesting that
cadherin-6 is the human counterpart of rat
K-cadherin. Expression of
cadherin-6 in various human normal tissues and
carcinoma cells was examined by Northern blot analysis using a specific probe corresponding to the signal and precursor sequence. Among normal tissues examined, brain, cerebellum, and kidney showed strong expression of
cadherin-6, whereas lung, pancreas, and gastric mucosa showed weak expression. Transcripts of
cadherin-6 were not detected in normal liver, whereas four of six
hepatocellular carcinoma cell lines examined expressed
cadherin-6 abundantly. As reported for rat
K-cadherin, three
renal carcinoma cell lines also expressed
cadherin-6 strongly. The most interesting finding was obtained for
small cell lung carcinoma lines. Among 15 of such cell lines examined, all of 11 cadherin-6-positive lines were classified into the classic type, whereas the negative cell lines were all of the variant type. The present results suggest that besides E- and
P-cadherin, other
cadherin molecules are expressed in human
cancers and are responsible for additional
biological properties of the
carcinoma cells.