Precious studies have shown that the expression of the cell-cell adhesion m
olecule (C-CAM1), located at chromosome 19, is down-regulated in several ty
pes of human cancers, including prostate and breast cancers. Two major isof
orms of C-CAM1, the long or L-form C-CAM1 and the short or S-form C-CAM1, a
re derived from the C-CAM1 gene through alternative splicing. Tumor cells t
ransfected with L-form C-CAM1, which contains a cytoplasmic domain, display
significantly lower growth rates and less tumorigenicity in both in vitro
and in vivo models compared with untransfected tumor cells, suggesting that
L-form C-CAM1 may be a tumor suppressor. The transfection of the cytoplasm
ic domain of L-form CCAM1 could also cause suppression of tumor growth, fur
ther supporting the role of L-form C-CAM1 in tumorigenesis. In contrast to
reports of most of the tumor types tested, Ohwada et al. (Am. J. Respir. Ce
ll Mel. Biol,, ZI: 214-220, 1994) reported that C-CAM1 was not down-regulat
ed or even up-regulated in lung cancer. Because the cytoplasmic domain of L
-form C-CAM1 is critical for the tumor suppressor function of C-CAM1, we hy
pothesized that switching of the isoform rather than down-regulation of C-C
AM1 gene expression occurs during lung tumorigenesis, To test this hypothes
is, we analyzed pairs of tumor tissue and corresponding normal-appearing lu
ng tissue from 51 patients with non-small cell lung cancer (NSCLC) and 43 c
ell lines to determine expression profiles of L-form C-CAM1 and S-form C-CA
M1 using reverse transcription-PCR. We found that L-form C-CAMI was the pre
dominant form (75%; 38 of 51) in normal-appearing lung tissue, whereas most
(84%; 43 of 51) of the primary NSCLC tissue samples expressed predominantl
y S-form C-CAMI (P < 0.0001), Similarly, 19 (79%) of the 24 NSCLC cell line
s and 17 (85%) of the 20 small cell lung cancer cell lines expressed predom
inantly S-form C-CAMI. The frequent alteration of the 6-CAM1 expression pat
tern suggests that C-CAM1 has an important role in lung tumorigenesis.