Abstract
The matrix-specific protein periostin (POSTN) is up-regulated in human cancers and associated with cancer growth, metastasis and angiogenesis. Although the stroma of cancer tissues is the main source of POSTN, it is still unclear how POSTN plays a role to facilitate the interplay between cancer cells and cancer-associated fibroblasts (CAFs) in head and neck cancer (HNC), thereby promoting tumorigenesis via modifying the tumor microenvironment. Herein, we have performed studies to investigate POSTN and its role in HNC microenvironment. Our results indicated that POSTN was significantly up-regulated in HNCs, especially in the tissues with lymph node metastasis. Moreover, POSTN was highly enriched in the stroma of cancer tissues and produced mainly by CAFs. More importantly, we have pinpointed TGF-β3 as the major upstream molecular that triggers the induction of POSTN in CAFs. As such, during the interaction between fibroblasts and cancer cells, the increased stromal POSTN induced by TGF-β3 directly accelerated the growth, migration and invasion of cancer cells. Hence, our study has provided a novel modulative role for POSTN on HNC progression and further reveals POSTN as an effective biomarker to predict metastasis as well as a potential cancer therapeutic target.
Highlights
Head and neck cancer (HNC) ranks sixth among malignancies worldwide[1]
To understand the nature of genes that are responsible for the pathological progression associated with head and neck cancer (HNC) development, we searched for the microarray data of squamous cell carcinoma from GEO datasets to
Consistent with previous studies[18,19], our data showed that POSTN was up-regulated in HNC and correlated with the tumor cell growth and metastasis
Summary
Head and neck cancer (HNC) ranks sixth among malignancies worldwide[1]. the living quality of patients with this devastating disease has been raised greatly, the 5-year survival rate of HNC patients has still remained unacceptable throughout the last 3 decades[2], especially in patients with locoregional lymph node metastases[3]. We investigated the expression level of POSTN in HNC and demonstrated the functional role of POSTN in the growth and metastasis of HNC cells. Western blotting was performed to investigate the protein levels of POSTN in HNC tissues and the results indicated that POSTN was highly expressed in cancer samples compared with adjacent normal tissues (Fig. 1D).
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