Possible involvement of TWIST in enhanced peritoneal metastasis of epithelial ovarian carcinoma.
Loss of E-cadherin triggers peritoneal dissemination, leading to an adverse prognosis for most patients with epithelial ovarian carcinoma (EOC). Because TWIST mainly regulates the epithelial-to-mesenchymal transition and is one of the E-cadherin repressors, we investigated the possibility that TWIST expression affects peritoneal metastasis of EOC using siRNA technique. In the present study, we showed a correlation between TWIST expression and EOC cellular morphology. Furthermore, we demonstrated that the suppression of TWIST expression in EOC cells (HEY) alters the cellular morphology from a fibroblastic and motile phenotype to an epithelial phenotype, and inhibits the adhesion of these cells to mesothelial monolayers. To investigate the mechanism by which down-regulation of TWIST leads to inhibition of adhesion to mesothelial cells (MCs), expression of adhesion molecules (CD29, CD44 and CD54) were observed. Moreover, matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase, important markers associated with invasive and metastatic potential, were remarkably reduced. This findings suggests that reduced expression of TWIST suppresses the multistep process of peritoneal dissemination (detachment from the primary lesion, adhesion to MCs and invasion of MCs) and may be a potential therapeutic target for the treatment of this carcinoma.
Terauchi
Mikio
M
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya, 466-8550, Japan.
Kajiyama
Hiroaki
H
Yamashita
Mamoru
M
Kato
Mikihiko
M
Tsukamoto
Hirohisa
H
Umezu
Tomokazu
T
Hosono
Satoyo
S
Yamamoto
Eiko
E
Shibata
Kiyosumi
K
Ino
Kazuhiko
K
Nawa
Akihiro
A
Nagasaka
Tetsuro
T
Kikkawa
Fumitaka
F
D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000378:metabolism* / Q000556:secondary; D051879:Twist-Related Protein 1 / Q000096:biosynthesis / Q000502:physiology*
D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D051879:Twist-Related Protein 1; D018799:Intercellular Adhesion Molecule-1; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14