Bone marrow mesenchymal stem cells promote head and neck cancer progression through Periostin-mediated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin.
Bone marrow mesenchymal stem cells (BMMSC) have been shown to be recruited to the tumor microenvironment and exert a tumor-promoting effect in a variety of cancers. However, the molecular mechanisms related to the tumor-promoting effect of BMMSC on head and neck cancer (HNC) are not clear. In this study, we investigated Periostin (POSTN) and its roles in the tumor-promoting effect of BMMSC on HNC. In vitro analysis of HNC cells cultured in BMMSC-conditioned media (MSC-CM) showed that MSC-CM significantly promoted cancer progression by enhancing cell proliferation, migration, epithelial-mesenchymal transformation (EMT), and altering expression of cell cycle regulatory proteins and inhibition of apoptosis. Moreover, MSC-CM promoted the expression of POSTN and POSTN promoted HNC progression through the activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. In a murine model of HNC, we found that BMMSC promoted tumor growth, invasion, metastasis and enhanced the expression of POSTN and EMT in tumor tissues. Clinical sample analysis further confirmed that the expression of POSTN and N-cadherin were correlated with pathological grade and lymph node metastasis of HNC. In conclusion, this study indicated that BMMSC promoted proliferation, invasion, survival, tumorigenicity and migration of head and neck cancer through POSTN-mediated PI3K/Akt/mTOR activation.
['Liu|Chuanxia|C|', 'Feng|Xiaoxia|X|', 'Wang|Baixiang|B|', 'Wang|Xinhua|X|', 'Wang|Chaowei|C|', 'Yu|Mengfei|M|', 'Cao|Guifen|G|', 'Wang|Huiming|H|http://orcid.org/0000-0001-5077-7481']
D000818:Animals D015815:Cell Adhesion Molecules D045744:Cell Line, Tumor D049109:Cell Proliferation D017077:Culture Media, Conditioned D018450:Disease Progression D058750:Epithelial-Mesenchymal Transition D015972:Gene Expression Regulation, Neoplastic D006258:Head and Neck Neoplasms D006801:Humans D059630:Mesenchymal Stem Cells D051379:Mice D009362:Neoplasm Metastasis D009367:Neoplasm Staging D009368:Neoplasm Transplantation D019869:Phosphatidylinositol 3-Kinases D051057:Proto-Oncogene Proteins c-akt D015398:Signal Transduction D058570:TOR Serine-Threonine Kinases D015854:Up-Regulation
bone marrow mesenchymal stem cells head and neck cancer Periostin PI3K/Akt/mTOR epithelial mesenchymal transition