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

Akiko Takahashi,Shigeki Umemura,Akihiko Gemma,Yuichiro Ohe,Hironobu Ohmatsu,Shingo Matsumoto,Koichi Goto,Atsushi Ochiai,Kanji Nagai,Hiroko Hashimoto,Tatsuya Yoshida,Shinya Neri,Seiji Niho,Kiyotaka Yoh,Genichiro Ishii,Shigeki Suzuki

doi:10.18632/oncotarget.3371

Akiko Takahashi, Shigeki Umemura + Show 14 more

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https://doi.org/10.18632/oncotarget.3371

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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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Cancer tissue is comprised of cancer cells, noncancerous cells, and extracellular matrix (ECM), and these components constitute specific microenvironments
We have reported that the presence of cancerassociated fibroblasts (CAFs) expressing PDPN is a predictor of a poor prognosis among patients with lung adenocarcinoma and squamous cell carcinoma of the lung, [22,23,24,25] and PDPN itself has been shown to exert tumor-promoting effects using in vitro and in vivo models
The current study showed that CAFs-PDPN suppressed the growth of small cell lung carcinoma (SCLC) using an in vitro co-culture model and surgically resected SCLC specimens

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Introduction

Cancer tissue is comprised of cancer cells, noncancerous cells, and extracellular matrix (ECM), and these components constitute specific microenvironments. Non-cancerous cell components include tumor-associated macrophages (TAMs), [1] immune cells, [2] and cancerassociated fibroblasts (CAFs). [2,3,4] Among the noncancerous cell components, CAFs reside near the cancer nests and are the most abundant constituent cells of a tumor. SCLC represents approximately 14%–20% of primary lung carcinomas [12,13,14] and has a more rapid doubling time; it exhibits the earlier development of widespread metastases. This disease is highly aggressive, and approximately 60%–70% of patients have disseminated disease at the time of diagnosis. Novel strategies are required for the treatment of SCLC

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