Podoplanin-expressing cancer-associated fibroblasts inhibit small cell lung cancer growth

// Akiko Takahashi 1, 2, 4 , Genichiro Ishii 1 , Shinya Neri 1 , Tatsuya Yoshida 1, 2 , Hiroko Hashimoto 1 , Shigeki Suzuki 1, 3 , Shigeki Umemura 2 , Shingo Matsumoto 2 , Kiyotaka Yoh 2 , Seiji Niho 2 , Koichi Goto 2 , Hironobu Ohmatsu 2 , Kanji Nagai 3 , Akihiko Gemma 4 , Yuichiro Ohe 5 , Atsushi Ochiai 1 1 Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan 2 Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan 3 Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan 4 Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Sendagi, Bunkyo City, Tokyo 113-0022, Japan 5 Division of Thoracic Oncology, National Cancer Center Hospital, Tsukiji, Chuo City, Tokyo 104-0045, Japan Correspondence to: Genichiro Ishii, e-mail: gishii@east.ncc.go.jp Keywords: podoplanin, small cell lung cancer, cancer-associated fibroblasts Received: December 10, 2014      Accepted: February 11, 2015      Published: March 24, 2015 ABSTRACT Cancer-associated fibroblasts (CAFs) expressing podoplanin (PDPN) are a favorable prognosticator in surgically resected small cell lung cancer (SCLC). Here we explore whether CAFs expressing PDPN influence proliferation of SCLC cells. Compared with control group (SCLC cells co-cultured with CAFs-Ctrl), numbers of SCLC cells co-cultured with CAFs overexpressing PDPN were decreased. Suppression of PDPN expression by shRNA in CAFs resulted in increased numbers of SCLC cells. In surgically resected human SCLC specimens, the frequency of Geminin-positive cancer cells was significantly higher in the cases with PDPN-positive CAFs than in the cases with PDPN-negative CAFs. Thus CAFs expressing PDPN inhibit growth of SCLC cells, suggesting that CAFs expressing PDPN represent a tumor inhibitory stromal cell component in SCLC.