TY - JOUR
T1 - Chorionic Gonadotropin-β Modulates Epithelial-Mesenchymal Transition in Colorectal Carcinoma Metastasis
AU - Kawamata, Futoshi
AU - Nishihara, Hiroshi
AU - Homma, Shigenori
AU - Kato, Yasutaka
AU - Tsuda, Masumi
AU - Konishi, Yuji
AU - Wang, Lei
AU - Kohsaka, Shinji
AU - Liu, Cheng
AU - Yoshida, Tadashi
AU - Tanino, Mishie
AU - Tanaka, Shinya
AU - Kawamura, Hideki
AU - Kamiyama, Toshiya
AU - Taketomi, Akinobu
N1 - Funding Information:
Supported by the Uehara Memorial Foundation Fellowship grant 201430015 (F.K.).
Publisher Copyright:
© 2018 American Society for Investigative Pathology
PY - 2018/1
Y1 - 2018/1
N2 - Ectopic production of free β human chorionic gonadotropin (hCGβ) has been associated with aggressive behavior in non-trophoblastic tumors. hCGβ shares common evolutionary sequences with transforming growth factor-β (TGF-β), which represents a major driving force of epithelial-to-mesenchymal transition (EMT). In this study, we examined the biological roles of hCGβ during EMT and its clinical significance in colorectal cancer (CRC) progression. Eighty CRC specimens and 54 preoperative serum samples were analyzed. hCGβ-overexpressing human CRC cell lines were examined for invasiveness and tumorigenicity, and the expression of EMT-associated genes was investigated. In human CRC, histologic hCGβ positivity [13/80 (16.3%)] was lower than serologic hCGβ positivity [13/54 (24.1%)]. However, it was significantly correlated with several clinicopathological features and unfavorable outcome (P < 0.05). hCGβ-overexpressing cell lines had increased invasiveness, migratory ability, and metastatic potential in mice (P < 0.01). Western blot, PCR, and microarray analyses showed hCGβ altered expression of EMT-related genes, including E-cadherin, phosphorylated SMAD2, SNAIL, and TWIST. hCGβ-induced SNAIL and TWIST overexpression levels were reversible by type I and type II TGF-β receptor inhibitors (P < 0.05). hCGβ thus induces EMT via the TGF-β signaling pathway, and it may represent a molecular target in CRC treatment.
AB - Ectopic production of free β human chorionic gonadotropin (hCGβ) has been associated with aggressive behavior in non-trophoblastic tumors. hCGβ shares common evolutionary sequences with transforming growth factor-β (TGF-β), which represents a major driving force of epithelial-to-mesenchymal transition (EMT). In this study, we examined the biological roles of hCGβ during EMT and its clinical significance in colorectal cancer (CRC) progression. Eighty CRC specimens and 54 preoperative serum samples were analyzed. hCGβ-overexpressing human CRC cell lines were examined for invasiveness and tumorigenicity, and the expression of EMT-associated genes was investigated. In human CRC, histologic hCGβ positivity [13/80 (16.3%)] was lower than serologic hCGβ positivity [13/54 (24.1%)]. However, it was significantly correlated with several clinicopathological features and unfavorable outcome (P < 0.05). hCGβ-overexpressing cell lines had increased invasiveness, migratory ability, and metastatic potential in mice (P < 0.01). Western blot, PCR, and microarray analyses showed hCGβ altered expression of EMT-related genes, including E-cadherin, phosphorylated SMAD2, SNAIL, and TWIST. hCGβ-induced SNAIL and TWIST overexpression levels were reversible by type I and type II TGF-β receptor inhibitors (P < 0.05). hCGβ thus induces EMT via the TGF-β signaling pathway, and it may represent a molecular target in CRC treatment.
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U2 - 10.1016/j.ajpath.2017.08.034
DO - 10.1016/j.ajpath.2017.08.034
M3 - Article
C2 - 29037859
AN - SCOPUS:85040172239
SN - 0002-9440
VL - 188
SP - 204
EP - 215
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -
