Periostin, a Cell Adhesion Molecule, Facilitates Invasion in the Tumor Microenvironment and Annotates a Novel Tumor-Invasive Signature in Esophageal Cancer

Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Cancer Research (Impact Factor: 9.33). 07/2010; 70(13):5281-92. DOI: 10.1158/0008-5472.CAN-10-0704
Source: PubMed


Human squamous cell cancers are the most common epithelially derived malignancies. One example is esophageal squamous cell carcinoma (ESCC), which is associated with a high mortality rate that is related to a propensity for invasion and metastasis. Here, we report that periostin, a highly expressed cell adhesion molecule, is a key component of a novel tumor-invasive signature obtained from an organotypic culture model of engineered ESCC. This tumor-invasive signature classifies with human ESCC microarrays, underscoring its utility in human cancer. Genetic modulation of periostin promotes tumor cell migration and invasion as revealed in gain-of-loss and loss-of-function experiments. Inhibition of epidermal growth factor receptor signaling and restoration of wild-type p53 function were each found to attenuate periostin, suggesting the interdependence of two common genetic alterations with periostin function. Collectively, our studies reveal periostin as an important mediator of ESCC tumor invasion and they indicate that organotypic (three-dimensional) culture can offer an important tool to discover novel biological effectors in cancer.

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    • "Furthermore, it is involved in remodeling the tumor microenvironment, which in turn promotes tumor survival, growth, and invasiveness [47]. This has also been described in the pancreatic parenchyma, in which periostin creates a tumor-supportive niche by sustaining fibrogenic stellate cell activity [17, 56], and in esophageal cancer, in which periostin facilitates tumor invasion [57, 58]. Stromal periostin has also been indicated to play a critical role in metastatic colonization [59–61], by regulating the interactions between cancer stem cells and their metastatic niche. "
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    • "POSTN has been shown to increase the metastatic potential of tumorigenic 293T cells in vivo as well as stimulating EMT (Yan and Shao, 2006). Moreover, our group has demonstrated the functional importance of POSTN in initiating tumour cell invasion when secreted at the invasive front through the convergence of mutant p53 and EGFR overexpression (Michaylira et al, 2010). Although it does not possess an Arginine–Glutamate–Aspartate (RGD) domain, a classical structural element for binding to integrins, POSTN also been reported to bind to a V b 5 and a V b 3 integrins to coactivate EGFR signalling that modulates cell motility and proliferation (Yan and Shao, 2006). "
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    ABSTRACT: Matricellular proteins have been classified as a family of non-structural matrix proteins capable of modulating a variety of biological processes within the extracellular matrix (ECM). These proteins are expressed dynamically and their cellular functions are highly dependent upon cues from the local environment. Recent studies have shown an increasing appreciation of the key roles these ECM proteins play within the tumour microenvironment. Induced by either tumour cells or tumour stromal components, matricellular proteins initiate downstream signalling events that lead to proliferation, invasion, matrix remodelling and dissemination to pre-metastatic niches in other organs. In this review, we summarise and discuss the current knowledge of the diverse roles these proteins play within the microenvironment that influences tumour progression and potential for future therapies targeting the tumour microenvironment.British Journal of Cancer advance online publication, 15 January 2013; doi:10.1038/bjc.2012.592
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    • "The correlation between periostin expression and poor prostate cancer patient outcome is consistent with previous studies that identified periostin overexpression in several invasive tumor types [25], [28], [29], [34]. Recently, periostin was found to promote invasiveness of esophageal carcinoma [35]. However, another study reported a downregulation of POSTN in lung cancer tissues indicating a potential context-dependent tumor suppressor activity of POSTN [33] that could be in line with the association of POSTN overexpression with good prognosis in breast cancer patients observed in the present study. "
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