Anterior gradient 2: A novel sensitive tumor marker for metastatic oral cancer

Chen, Yi Ting; Ho, Chung Liang; Chen, Po Ku; Chen, Yuh Ling; Chang, Chuan Fa

doi:10.1016/j.canlet.2013.06.025

Cited by 20 publications

(16 citation statements)

References 34 publications

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“…Although mRNA and DNA copy numbers of AGR2 in HNSCC were not as significant as in other cancers. The protein expression of AGR2 in human HNSCC was consistent with the DNA copy number and the mRNA level, as indicated in this study as well as in other studies [ 14 , 16 ]. The present study is the first report that described abnormal AGR2 expression in HNSCC with radiotherapy and chemotherapy.…”

Section: Discussionsupporting

confidence: 91%

“…This phenomenon may mirror the developmentally regulated EMT pathways, including Wnt, Notch, and Hedgehog, which also show CSC self-renewal and maintenance [ 30 , 31 ]. A recent report indicated that AGR2 enhanced in vitro cell invasion and metastasis in HNSCC [ 14 ], Thus, we hypothesized that AGR2 might enhance cancer invasion by increasing EMT. Similar reports indicated that AGR2 could promote cellular proliferation and metastasis of HNSCC [ 16 ].…”

Section: Discussionmentioning

confidence: 97%

“…Emerging evidences showed that abnormal expression of AGR2 might be involved in tumorigenesis and progression of human cancers, such as prostate, breast, ovarian, esophagus, gastro-intestinal tract, and lung cancers, as reviewed by Brychtova et al in Ref [ 13 ]. Increased AGR2 expression contributes to metastasis because of its capacity to enhance migration of breast cancer and oral squamous cell carcinoma in vitro and in vivo [ 14 - 16 ]. Recent reports showed that aberrant AGR2 expression helps breast cancer cells survive under serum-depleted conditions and/or hypoxic culture conditions, promotes angiogenesis, and increases cell invasion [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Anterior gradient protein 2 expression in high grade head and neck squamous cell carcinoma correlated with cancer stem cell and epithelial mesenchymal transition

Wang

Huang

et al. 2015

Oncotarget

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Anterior gradient protein 2 (AGR2) is a novel biomarker with potential oncogenic role. We sought to investigate the diagnostic and prognostic role of AGR2 on head and neck squamous cell carcinoma (HNSCC) with an emphasis on its correlation of cancer stemloid cells (CSC) and epithelial mesenchymal transition (EMT). We found that AGR2 protein levels were higher in HNSCC than in normal oral mucosa. High levels of AGR2 were associated with the T category, pathological grade and lymph node metastasis of HNSCC. Expression of AGR2 increased in recurring HNSCC after radiotherapy and in post cisplatin-based chemotherapeutic tissues. In HNSCC cell lines, knock-down of AGR2 induced apoptosis, reduced sphere formation, and down-regulated Survivin, Cyclin D1, Bcl2, Bcl2l1, Slug, Snail, Nanog and Oct4. In addition, over-expressed AGR2 in transgenic mice with spontaneous HNSCC was associated with lost function of Tgfbr1 and/or lost function of Pten. In vitro knockdown TGFBR1 in HNSCC cell lines increased AGR2 expression. These results suggest that AGR2 is involved in EMT and self-renewal of CSC and may present a potential therapeutic target (oncotarget) for HNSCC.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Anterior gradient protein 2 expression in high grade head and neck squamous cell carcinoma correlated with cancer stem cell and epithelial mesenchymal transition

Wang

Huang

et al. 2015

Oncotarget

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“…Gastric SRCC cells also followed the preceding fibroblasts in the gel-invasion assay performed in this study, suggesting that fibroblasts activated by extracellular Agr2 may lead to cancer cell invasion. High expression of Agr2 is correlated with metastasis of some types of cancer (33,38). Thus, in addition to the cell-autonomous effects of Agr2 on cancer cells, fibroblastassociated cancer invasion mediated by extracellular Agr2 may play a pivotal role in cancer metastasis.…”

Section: Discussionmentioning

confidence: 99%

Agr2 Mediates Paracrine Effects on Stromal Fibroblasts That Promote Invasion by Gastric Signet-Ring Carcinoma Cells

et al. 2015

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Agr2 is a disulfide isomerase residing in the endoplasmic reticulum (ER), which physiologically regulates protein folding and mediates resistance to ER stress. Agr2 is overexpressed in adenocarcinomas of various organs, where it participates in neoplastic transformation and metastasis, therefore acts as a pro-oncogenic protein. Besides its normal localization in the ER, Agr2 is also found in the serum and urine of cancer patients, although the physiological significance of extracellular Agr2 is poorly understood. In this study, we demonstrated that extracellular Agr2 can activate stromal fibroblasts and promote fibroblastassociated cancer invasion in gastric signet-ring cell carcinoma (SRCC), where Agr2 is highly expressed. Agr2 secreted from SRCC cells was incorporated by the surrounding gastric fibroblasts and promoted invasion by these cells. In turn, activated fibroblasts coordinated the invasive behavior of fibroblasts and cancer cells. Our findings suggested that Agr2 drives progression of gastric SRCC by exerting paracrine effects on fibroblasts in the tumor microenvironment, acting also to increase the growth and resistance of SRCC cells to oxidative and hypoxic stress as cell autonomous effects. Cancer Res; 75(2); 356-66. Ó2014 AACR.

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“…In esophageal cancer, AGR2 can be used to improve distinguishing adenocarcinoma (99 % positive) from squamous cell carcinoma (37 % positive, typically in focal areas) in some circumstances [ 10 ]. However, oral squamous cell carcinoma has recently been reported to express AGR2 [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

High expression of AGR2 in lung cancer is predictive of poor survival

et al. 2015

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BackgroundAnterior gradient 2 (AGR2) is a protein disulfide isomerase-like protein widely expressed in many normal tissues as well as cancers. In our study, non-neoplastic bronchial epithelial cells as well as non-small cell lung cancer (NSCLC) cells express AGR2 protein.MethodsAGR2 expression was analyzed on lung tissue microarrays. Tumor staining was correlated with clinical outcomes.ResultsOn a lung cancer tissue microarray using immunohistochemistry, expression levels in cancer showed generally decreasing intensities in order from adenocarcinomas with mucinous components, other adenocarcinomas, squamous carcinomas, to large cell carcinomas. The study cohort was comprised of 400 cases. As a group, there was a slight trend of lower expression with increasing tumor grade. AGR2 expression level was a significant predictor of overall survival in younger patients only. Patients under 65 with lower levels showed a significantly better survival for both men and women. Patients over 65, in contrast, showed no such trend.ConclusionsNearly all NSCLC tumors show AGR2 expression. Lung cancer expression of AGR2 has prognostic value for younger patients.

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Anterior gradient 2: A novel sensitive tumor marker for metastatic oral cancer

Cited by 20 publications

References 34 publications

Anterior gradient protein 2 expression in high grade head and neck squamous cell carcinoma correlated with cancer stem cell and epithelial mesenchymal transition

Anterior gradient protein 2 expression in high grade head and neck squamous cell carcinoma correlated with cancer stem cell and epithelial mesenchymal transition

Agr2 Mediates Paracrine Effects on Stromal Fibroblasts That Promote Invasion by Gastric Signet-Ring Carcinoma Cells

High expression of AGR2 in lung cancer is predictive of poor survival

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