Podoplanin-expressing cancer-associated fibroblasts inhibit small cell lung cancer growth
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Akiko Takahashi1,2,4, Genichiro Ishii1, Shinya Neri1, Tatsuya Yoshida1,2, Hiroko Hashimoto1, Shigeki Suzuki1,3, Shigeki Umemura2, Shingo Matsumoto2, Kiyotaka Yoh2, Seiji Niho2, Koichi Goto2, Hironobu Ohmatsu2, Kanji Nagai3, Akihiko Gemma4, Yuichiro Ohe5, Atsushi Ochiai1
1Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan
2Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan
3Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan
4Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Sendagi, Bunkyo City, Tokyo 113-0022, Japan
5Division of Thoracic Oncology, National Cancer Center Hospital, Tsukiji, Chuo City, Tokyo 104-0045, Japan
Genichiro Ishii, e-mail: [email protected]
Keywords: podoplanin, small cell lung cancer, cancer-associated fibroblasts
Received: December 10, 2014 Accepted: February 11, 2015 Published: March 24, 2015
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.
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