Gabrielle Wong

We describe a novel imaging strategy that detects early stage esophageal squamous cell carcinoma (ESCC) when combined with endoscopic approaches that could help improve clinical outcomes. We had previously identified Periostin as an integrin-binding protein that is important in the tumor microenvironment. We created a fluorescent-labeled antibody that recognizes periostin and binds specifically to ESCC xenograft tumors in mice. In L2-cre;p120ctnLoxP/LoxP mice, which develop squamous cell… Show more

We describe a novel imaging strategy that detects early stage esophageal squamous cell carcinoma (ESCC) when combined with endoscopic approaches that could help improve clinical outcomes. We had previously identified Periostin as an integrin-binding protein that is important in the tumor microenvironment. We created a fluorescent-labeled antibody that recognizes periostin and binds specifically to ESCC xenograft tumors in mice. In L2-cre;p120ctnLoxP/LoxP mice, which develop squamous cell cancers that resemble human ESCC, we visualized the probe in preneoplastic and neoplastic esophageal lesions using near-infrared fluorescent imaging with upper-gastrointestinal endoscopy. Periostin might be a biomarker of the esophageal tumor microenvironment that can be used to detect preneoplastic lesions. Show less

Mini review of matricellular proteins and theirr roles in promoting tumor growth and metastasis through facilitating protein-protein interactions within the tumor microenvironment

We had previously described that matricellular protein, periostin (POSTN) as important for invasion in ESCC tumor microenvironment. In this study, we observe that the inducible knockdown of POSTN decreases esophageal squamous cell carcinoma (ESCC) tumor growth in vivo and demonstrate that POSTN cooperates with a conformational missense p53 mutation to enhance invasion. Pathway analyses reveal that invasive esophageal cells expressing POSTN and p53(R175H) mutation display activation of signal… Show more

We had previously described that matricellular protein, periostin (POSTN) as important for invasion in ESCC tumor microenvironment. In this study, we observe that the inducible knockdown of POSTN decreases esophageal squamous cell carcinoma (ESCC) tumor growth in vivo and demonstrate that POSTN cooperates with a conformational missense p53 mutation to enhance invasion. Pathway analyses reveal that invasive esophageal cells expressing POSTN and p53(R175H) mutation display activation of signal transducer and activator of transcription 1 (STAT1) target genes, suggesting that the induction of STAT1 and STAT1-related genes could foster a permissive microenvironment that facilitates invasion of esophageal epithelial cells into the extracellular matrix. Furthermore, we find that STAT1 is activated in ESCC xenograft tumors, but this activation is attenuated with inducible knockdown of POSTN in ESCC tumors. Overall, these results highlight the novel molecular mechanisms supporting the capacity of POSTN in mediating tumor invasion during ESCC development and have implications of therapeutic strategies targeting the tumor microenvironment. Show less

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 engineeredesophageal squamous cell carcinoma (ESCC). This tumor-invasive signature classifies with human ESCC microarrays, and 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… Show more

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 engineeredesophageal squamous cell carcinoma (ESCC). This tumor-invasive signature classifies with human ESCC microarrays, and 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, we demostrate periostin as an important mediator of ESCC tumor invasion and indicate that organotypic (three-dimensional) culture can offer an important tool to discover novel biological effectors in cancer. Show less