TGFβ3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis

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.

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

“…POSTN plays a functional role in the regeneration of tissues such as bone and heart, promotes wound healing and is frequently up‐regulated in various types of human cancers and is implicated in cancer cell proliferation, invasion, and metastasis . However, whether POSTN is associated with the effect of BMMSC on HNC had not yet been previously addressed.…”

“…POSTN plays a functional role in the regeneration of tissues such as bone and heart, promotes wound healing and is frequently upregulated in various types of human cancers and is implicated in cancer cell proliferation, invasion, and metastasis. 31,32 However, whether POSTN is associated with the effect of BMMSC on HNC had not yet been previously addressed. In this study, we found that MSC-CM could promote the expression of POSTN possibly because BMMSC could secrete many kinds of cytokines into MSC-CM such as interleukin-6 (IL-6), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-b) etc.…”

Periostin function in communication with extracellular matrices

“…Pathologically, periostin has also been localized in infarcted myocardium Oka et al 2007), fibrosis (Okamoto et al 2011;Ishikawa et al 2014;Naik et al 2012;Takayama et al 2006;Uchida et al 2012), tissues undergoing wound healing (Nishiyama et al 2011;Norris et al 2007;Ontsuka et al 2012;Zhou et al 2010), and cancer-associated stroma (Fukushima et al 2008;Kashima et al 2009;Kikuchi et al 2008Kikuchi et al , 2014Liu et al 2014;Nitsche et al 2016;Oskarsson and Massague 2012;Qin et al 2016;Ruan et al 2009;Sung et al 2016;Tian et al 2015;Underwood et al 2015;Wang and Ouyang 2012). Taken together, periostin expression is well correlated with tissue regeneration (Conway et al 2014).…”

Upregulation of Periostin Prevents High Glucose-Induced Mitochondrial Apoptosis in Human Umbilical Vein Endothelial Cells via Activation of Nrf2/HO-1 Signaling

“…For instance, periostin promotes the secretion of fibronectin from fibroblasts and participates in extracellular matrix remodeling [18]. It has been reported that periostin modulates head and neck cancer growth and metastasis [19]. In tumor microenvironment, periostin shows the ability to regulate many aspects of endothelial cells, facilitating tumor angiogenesis [20].…”