Bone marrow mesenchymal stem cells promote head and neck cancer progression through Periostin mediated PI3K/AKT/mTOR

Abstract

Bone marrow mesenchymal stem cells (BMMSCs) have been shown to be recruited to tumor microenvironment and exert a tumor-promoting effect in a variety of cancers. However, the molecular mechanisms related to the tumor-promoting effect of BMMSCs on head and neck cancer (HNC) were not clear. In this study, we investigated Periostin (POSTN) and its roles in tumor-promoting effect of BMMSCs on HNC. In vitro analysis of HNC cells cultured in BMMSCs conditioned media (MSC-CM) showed that MSC-CM significantly promoted the cancer progression by enhancing cell proliferation, migration, epithelial-mesenchymal transformation (EMT), 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 PI3K/AKT/mTOR signaling pathway. In a murine model of HNC, we found that BMMSCs promoted the tumor growth, invasion, metastasis and enhanced the expression of POSTN and EMT in tumor tissues. Clinical samples 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 BMMSCs promoted proliferation, invasion, survival, tumorigenicity and migration of head and neck cancer through POSTN mediated PI3K/AKT/mTOR activation.

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