TY - JOUR
T1 - NSAIDs suppress the expression of claudin-2 to promote invasion activity of cancer cells
AU - Mima, Shinji
AU - Takehara, Masaya
AU - Takada, Hiroko
AU - Nishimura, Tomoko
AU - Hoshino, Tatsuya
AU - Mizushima, Tohru
N1 - Funding Information:
Grants-in-Aid of Scientific Research from the Ministry of Health, Labour, and Welfare of Japan, Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and Grants-in-Aid of the Japan Science and Technology Agency.
PY - 2008
Y1 - 2008
N2 - Non-steroidal anti-inflammatory drugs (NSAIDs) show chemopreventive effects; however, the precise molecular mechanism of these effects is still unclear. On the other hand, the expression of proteins that form tight junctions (TJs) (such as claudins) in clinically isolated tumors is frequently altered relative to normal tissue. We previously reported that NSAIDs upregulate the expression of claudin-4 and that this upregulation contributes to NSAID-dependent inhibition of both migration activity and anchorage-independent growth of cancer cells. In the current study, we have systematically examined the effects of various NSAIDs on the expression of various TJ proteins and have found that NSAIDs specifically and drastically inhibit the expression of claudin-2. Overexpression or suppression of claudin-2 expression caused stimulation or inhibition, respectively, of the invasion and migration activity of cancer cells. Furthermore, NSAIDs inhibited the invasion and migration activity of cancer cells and this inhibition was suppressed by overexpression of claudin-2. In contrast, neither cell growth nor apoptosis induced by lack of anchorage of cancer cells was affected by overexpression or suppression of expression of claudin-2. These results suggest that inhibition of claudin-2 expression by NSAIDs contributes to NSAID-dependent inhibition of invasion of cancer cells in vitro and that it may be involved in the chemopreventive effects of NSAIDs by inhibiting metastasis in vivo.
AB - Non-steroidal anti-inflammatory drugs (NSAIDs) show chemopreventive effects; however, the precise molecular mechanism of these effects is still unclear. On the other hand, the expression of proteins that form tight junctions (TJs) (such as claudins) in clinically isolated tumors is frequently altered relative to normal tissue. We previously reported that NSAIDs upregulate the expression of claudin-4 and that this upregulation contributes to NSAID-dependent inhibition of both migration activity and anchorage-independent growth of cancer cells. In the current study, we have systematically examined the effects of various NSAIDs on the expression of various TJ proteins and have found that NSAIDs specifically and drastically inhibit the expression of claudin-2. Overexpression or suppression of claudin-2 expression caused stimulation or inhibition, respectively, of the invasion and migration activity of cancer cells. Furthermore, NSAIDs inhibited the invasion and migration activity of cancer cells and this inhibition was suppressed by overexpression of claudin-2. In contrast, neither cell growth nor apoptosis induced by lack of anchorage of cancer cells was affected by overexpression or suppression of expression of claudin-2. These results suggest that inhibition of claudin-2 expression by NSAIDs contributes to NSAID-dependent inhibition of invasion of cancer cells in vitro and that it may be involved in the chemopreventive effects of NSAIDs by inhibiting metastasis in vivo.
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U2 - 10.1093/carcin/bgn134
DO - 10.1093/carcin/bgn134
M3 - Article
C2 - 18586689
AN - SCOPUS:53349160180
VL - 29
SP - 1994
EP - 2000
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 10
ER -