Mesenchymal stem cells derived from normal gingival tissue inhibit the proliferation of oral cancer cells in vitro and in vivo.
The interplay between tumor cells and mesenchymal stem cells (MSCs) within tumor microenvironment plays a significant role in tumor development, and thus might be exploited for therapeutic intervention. In this study, we isolated MSCs from normal gingival tissue (GMSCs), and detected the effect of GMSCs on oral cancer cells via direct co-culture and indirect co-culture systems. The cell proliferation assay of direct co-culture showed that GMSCs could inhibit the growth of oral cancer cells. Conditioned medium derived from GMSCs (GMSCs-CM) also exerted an anticancer effect, which indicates that soluble factors in GMSCs-CM played a dominant role in GMSCs-induced cancer cell growth inhibition. To investigate the mechanism, we performed apoptosis assay by flow cytometry, and confirmed that cancer cell apoptosis induced by GMSCs could be a reason for the effect of GMSCs on the growth of oral cancer cells. Western blotting also confirmed that GMSCs could upregulate expression of pro-apoptotic genes including p-JNK, cleaved PARP, cleaved caspase-3, Bax expression and downregulate proliferation- and anti-apoptosis-related gene expression such as p-ERK1/2, Bcl-2, CDK4, cyclin D1, PCNA and survivin. Importantly, the inhibitory effect of GMSCs on cancer cells can partially be restored by blockade of JNK pathway. Moreover, animal studies showed that GMSCs exerted an anticancer effect after oral cancer cells and GMSCs were co-injected with oral cancer cells. Taken together, our data suggest that GMSCs can suppress oral cancer cell growth in vitro and in vivo via altering the surrounding microenvironment of oral cancer cells, which indicates that GMSCs have a potential use in the management of oral dysplasia and oral cancer in future.
Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Xiaoli
X
Ji
Department of Stomatology, Peking University Third Hospital, Haidian, Beijing 100191, P.R. China.
Zhihui
Z
Zhang
Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Ying
Y
Han
Department of Stomatology, Wuhan Union Hospital, Wuhan, Hubei 430022, P.R. China.
Jiangyuan
J
Song
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Xiangliang
X
Xu
Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Jianqiu
J
Jin
Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Sha
S
Su
Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Dongdong
D
Mu
Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Xiaodan
X
Liu
Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Si
S
Xu
Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Hongwei
H
Cui
Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Zhongfang
Z
Zhao
Central Laboratory, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Yixiang
Y
Wang
Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China.
Hongwei
H
Liu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005434:Flow Cytometry; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D017077:Culture Media, Conditioned