Chorionic Gonadotropin-β Modulates Epithelial-Mesenchymal Transition in Colorectal Carcinoma Metastasis

Futoshi Kawamata, Hiroshi Nishihara, Shigenori Homma, Yasutaka Kato, Masumi Tsuda, Yuji Konishi, Lei Wang, Shinji Kohsaka, Cheng Liu, Tadashi Yoshida, Mishie Tanino, Shinya Tanaka, Hideki Kawamura, Toshiya Kamiyama, Akinobu Taketomi

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Abstract

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.

Original languageEnglish
Pages (from-to)204-215
Number of pages12
JournalAmerican Journal of Pathology
Volume188
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Kawamata, F., Nishihara, H., Homma, S., Kato, Y., Tsuda, M., Konishi, Y., Wang, L., Kohsaka, S., Liu, C., Yoshida, T., Tanino, M., Tanaka, S., Kawamura, H., Kamiyama, T., & Taketomi, A. (2018). Chorionic Gonadotropin-β Modulates Epithelial-Mesenchymal Transition in Colorectal Carcinoma Metastasis. American Journal of Pathology, 188(1), 204-215. https://doi.org/10.1016/j.ajpath.2017.08.034