Takahashi Akiko, Ishii Genichiro, Neri Shinya, Yoshida Tatsuya, Hashimoto Hiroko, Suzuki Shigeki, Umemura Shigeki, Matsumoto Shingo, Yoh Kiyotaka, Niho Seiji, Goto Koichi, Ohmatsu Hironobu, Nagai Kanji, Gemma Akihiko, Ohe Yuichiro, Ochiai Atsushi
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.
Oncotarget. 2015 Apr 20;6(11):9531-41. doi: 10.18632/oncotarget.3371.
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.
表达血小板反应蛋白1的癌症相关成纤维细胞（CAFs）是手术切除的小细胞肺癌（SCLC）的一个良好预后指标。在此，我们探讨表达血小板反应蛋白1的CAFs是否影响SCLC细胞的增殖。与对照组（SCLC细胞与CAFs-Ctrl共培养）相比，与过表达血小板反应蛋白1的CAFs共培养的SCLC细胞数量减少。通过短发夹RNA（shRNA）抑制CAFs中血小板反应蛋白1的表达导致SCLC细胞数量增加。在手术切除的人类SCLC标本中，血小板反应蛋白1阳性CAFs的病例中Geminin阳性癌细胞的频率显著高于血小板反应蛋白1阴性CAFs的病例。因此，表达血小板反应蛋白1的CAFs抑制SCLC细胞的生长，表明表达血小板反应蛋白1的CAFs代表SCLC中一种肿瘤抑制性基质细胞成分。
