Zilong Yan1, Kenoki Ohuchida2,3, Biao Zheng1,4, Takashi Okumura1, Shin Takesue1, Hiromichi Nakayama1, Chika Iwamoto5, Koji Shindo1, Taiki Moriyama1, Kohei Nakata1, Yoshihiro Miyasaka1, Takao Ohtsuka1, Kazuhiro Mizumoto6, Yoshinao Oda7, Makoto Hashizume5, Masafumi Nakamura1. 1. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan. 2. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan. kenoki@surg1.med.kyushu-u.ac.jp. 3. Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kenoki@surg1.med.kyushu-u.ac.jp. 4. Department of General Surgery, Shenzhen University General Hospital, Shenzhen, China. 5. Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 6. Cancer Center, Kyushu University Hospital, Fukuoka, Japan. 7. Department of Anatomical Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract
PURPOSE: This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer. METHODS: We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin-CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model. RESULTS: CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK-MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model. CONCLUSIONS: CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis.
PURPOSE: This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer. METHODS: We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin-CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model. RESULTS:CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK-MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model. CONCLUSIONS:CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis.
Authors: Maria L Lozano; Cristina Segú-Vergés; Mireia Coma; María T Álvarez-Roman; José R González-Porras; Laura Gutiérrez; David Valcárcel; Nora Butta Journal: Int J Mol Sci Date: 2021-06-27 Impact factor: 5.923
Authors: Moran Amit; Tongxin Xie; Frederico O Gleber-Netto; Patrick J Hunt; Gautam U Mehta; Diana Bell; Deborah A Silverman; Ismail Yaman; Yi Ye; Jared K Burks; Gregory N Fuller; Paul W Gidley; Marc-Elie Nader; Shaan M Raza; Franco DeMonte Journal: J Exp Clin Cancer Res Date: 2022-10-04