Bone marrow mesenchymal stem cells promote head and neck cancer progression through Periostin‐mediated phosphoinositide 3‐kinase/Akt/mammalian target of rapamycin

• Published in: Cancer science Vol. 109; no. 3; pp. 688 - 698
• Main Authors: Liu, Chuanxia, Feng, Xiaoxia, Wang, Baixiang, Wang, Xinhua, Wang, Chaowei, Yu, Mengfei, Cao, Guifen, Wang, Huiming
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.03.2018; John Wiley and Sons Inc
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animal models; Animals; Apoptosis; Biomarkers; Bone marrow; bone marrow mesenchymal stem cells; Breast cancer; Cadherins; Cell adhesion & migration; Cell Adhesion Molecules; Cell cycle; Cell Line, Tumor; Cell migration; Cell Proliferation; Culture Media, Conditioned - pharmacology; Cytokines; Disease Progression; Epithelial-Mesenchymal Transition; Ethics; Fibroblasts; Gene Expression Regulation, Neoplastic; Growth factors; Head & neck cancer; head and neck cancer; Head and Neck Neoplasms - metabolism; Humans; Kinases; Laboratory animals; Lymph nodes; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Metastases; Metastasis; Mice; Molecular modelling; Neoplasm Metastasis; Neoplasm Staging; Neoplasm Transplantation; Original; Ovarian cancer; Penicillin; Periostin; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt/mTOR; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rapamycin; Regulatory proteins; Signal Transduction; Stem cell transplantation; Stem cells; TOR protein; TOR Serine-Threonine Kinases - metabolism; Tumorigenicity; Tumors; Up-Regulation; United States > US; China; epithelial mesenchymal transition; head and neck cancer; bone marrow mesenchymal stem cells; PI3K/Akt/mTOR; Periostin
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13479

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. Bone marrow mesenchymal stem cells promoted proliferation, invasion, survival, tumorigenicity and migration of head and neck cancer through Periostin‐mediated PI3K/Akt/mTOR activation.