title: Podoplanin-expressing cancer-associated fibroblasts inhibit small cell lung cancer growth.
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.
authors.affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.|Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.|Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Sendagi, Bunkyo City, Tokyo 113-0022, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Neri
authors.affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.|Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.|Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Umemura
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Yoh
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Niho
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ohmatsu
authors.affiliation: Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Sendagi, Bunkyo City, Tokyo 113-0022, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital, Tsukiji, Chuo City, Tokyo 104-0045, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000368:Aged; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D064248:Geminin / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006085:Graft Survival; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017154:Stromal Cells / Q000502:physiology*; D014162:Transfection; D047368:Tumor Burden; D059016:Tumor Microenvironment / Q000502:physiology*; D000098853:Podoplanin
chemical_list: D064248:Geminin; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C577995:GMNN protein, human; C117468:PDPN protein, human; D000098853:Podoplanin
keywords: cancer-associated fibroblasts; podoplanin; small cell lung cancer