B7-H3 is Overexpressed in Patients Suffering Osteosarcoma and Associated with Tumor Aggressiveness and Metastasis

Wang, Ling; Zhang, Qi; Chen, Wei; Shan, Baoen; Ding, Yang; Zhang, Guochuan; Cao, Nana; Liu, Lei; Zhang, Yingze

doi:10.1371/journal.pone.0070689

Cited by 134 publications

(143 citation statements)

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“…Several studies reported that B7-H3 promoted tumor invasion and metastasis in cutaneous melanoma (30), osteosarcoma (25), and non-small cell lung cancer (31). In this study, we found that both the cell migratory and invasive potential in the B7-H3 knockdown groups of Maver and Z138 cells was reduced compared to the NC groups.…”

Section: Discussionsupporting

confidence: 51%

“…Tekle et al demonstrated that the B7-H3 silencing reduced metastatic capacity of MDA-MB-435 melanoma cells and significantly increased the survival of nude mice (20). Other studies also reported that B7-H3 was important in regulating the adhesive, migratory, and invasive capacity in breast cancer (21), glioblastoma (22), pancreatic cancer (23), prostate cancer (24) and osteosarcoma (25). Liu et al discovered that silencing of B7-H3 sensitized the breast cancer cell lines to paclitaxel by abrogating Jak2/Stat3 phosphorylation (26).…”

Section: Introductionmentioning

confidence: 99%

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B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity

Zhang

Wang

et al. 2015

International Journal of Oncology

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Abstract. B7-H3 (CD276), known as a member of B7 immunoregulatory family, is a type I transmembrane glycoprotein aberrantly expressed in numerous types of cancer and associated with poor prognosis. However, the role of B7-H3 in oncogenesis and chemosensitivity of mantle cell lymphoma (MCL) remains unknown. We determined the effects of downregulating B7-H3 expression on tumor progression and the sensitivity of chemotherapeutic drug in mantle cell lymphoma. B7-H3 knockdown was performed using lentivirus transduction in the Maver and Z138 mantle cell lymphoma cell lines, respectively. The effects of B7-H3 on cell proliferation, cycle, migration and invasion were investigated by CCK-8 assay, methyl cellulose colony forming assay, PI staining, and Transwell assays in vitro. By establishing Maver and Z138 xenograft models, the effects of B7-H3 on tumorigenicity were observed, and Ki-67 and PCNA was detected by immunohistochemistry. The downregulation of B7-H3 significantly decreased tumor proliferation in MCL in vitro and in vivo. In the B7-H3 knockdown groups of Maver and Z138 xenograft models, the mean inhibition rate of tumor growth was 59.1 and 65.0% (p=0.010 and 0.003), and the expression of both Ki-67 and PCNA were significantly lower, respectively. After B7-H3 silencing, the cell cycles of Maver and Z138 were both arrested at G0/G1 phase, and the cell migration rates and invasion capacity were decreased as well. Moreover, the impacts of B7-H3 RNAi on the antitumor effect of chemotherapy drugs were determined with CCK-8 and Annexin V-FITC/PI assays in vitro and with xenograft models in vivo. The silencing of B7-H3 increased the sensitivity of Maver and Z138 cells to rituximab and bendamustine and enhanced the drug-induced apoptosis, respectively. Our study demonstrates for the first time that B7-H3 promotes mantle cell lymphoma progression and B7-H3 knockdown significantly enhances the chemosensitivity. This may provide a new therapeutic approach to mantle cell lymphoma. IntroductionMantle cell lymphoma (MCL), a heterogeneous subtype of B-cell non-Hodgkin lymphoma (NHL), accounts for ~7% of NHL cases in the USA and Europe and has one of the worst outcomes of all the lymphomas (1,2). It is characterized by the t(11;14) (q13;q32) translocation, which results in overexpression of cyclin D1 and deregulation of the cell cycle (2). At initial diagnosis, most patients with the median age ~68-70 years have advanced stage disease, and the median overall survival is 3-5 years (3). Although several novel agents have proven to be effective, MCL remains a largely incurable disease and the following relapse is still challenging. Therefore, understanding the molecular mechanisms of MCL pathogenesis and drug resistance will aid in the development of highly active targeted therapies for the disease.B7-H3, a new member of B7 immunoregulatory family with immunoglobulin-like structure (4), is induced in activated dendritic cells, monocytes and T cells (5). Aberrant expression of B7-H3 has been reported and associated with poor prog...

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity

Zhang

Wang

et al. 2015

International Journal of Oncology

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“…In more recent studies of patients with prostate cancer, tumor B7-H3 expression was strongly correlated with disease spread at time of surgery, increased risk of clinical cancer recurrence, and cancer-specific death (20,21). Moreover, tumor B7-H3 expression was correlated with poor patient survival in clear cell renal cell carcinoma, urothelial cell carcinoma (22,23), ovarian cancer (24), glioblastoma (25), osteosarcoma (26), pancreatic cancer (27), and neuroblastoma (28). A few earlier reports have also implicated a positive immunologic function of B7-H3; e.g.…”

mentioning

confidence: 98%

“…Based on the mouse B7-H3 crystal structure, the FG loop of the IgV domain was identified to play a critical role in its T cell inhibitory function (33). B7-H3 is widely expressed among solid tumors, including prostate (20,21), renal cell carcinoma, urothelial cell carcinoma (22,23), ovarian cancer (24), glioblastoma (25), osteosarcoma (26), neuroblastoma (28), diffuse intrinsic pontine glioma (34), mesothelioma (35), and pancreatic cancer (27).…”

mentioning

confidence: 99%

Humanized Affinity-matured Monoclonal Antibody 8H9 Has Potent Antitumor Activity and Binds to FG Loop of Tumor Antigen B7-H3

Ahmed

Cheng

Zhao

et al. 2015

Journal of Biological Chemistry

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Background: B7-H3 is an immune inhibitory ligand and an antigen on many solid tumors. Results: Antibody 8H9 was humanized and affinity-matured, and its epitope was mapped to the FG loop of B7-H3. Conclusion: hu8H9 antibodies had potent antitumor activity and may modulate immune inhibitory properties of B7-H3. Significance: Antibodies were developed to target solid tumors and affect immune checkpoint blockade.

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“…CD276 was a tumorassociated antigen and it played a significant role in promoting migration and invasion of cancer cells [35,36]. Importantly, overexpression of CD276 was observed in various cancers including gastric cancer [37][38][39]. It suggested that downregulation of miR-940 in gastric tumor tissues might lead to overexpression of CD276 and further contribute to metastasis of gastric cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Plasma miR-940 may serve as a novel biomarker for gastric cancer

et al. 2015

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It was reported that circulating microRNAs could be applied as non-invasive biomarkers for cancer monitoring. The purpose of this study was to identify plasma miRNA that may serve as a novel biomarker for gastric cancer and to evaluate its clinical application. MicroRNA profiles were generated from plasma samples of 5 patients with gastric cancer (GC) versus 5 healthy controls (HC). MicroRNA-940 (miR-940) was one of the most downregulated miRNAs with fold change of 0.164. It was revealed that the expression of miR-940 was downregulated in both the initial set (N = 30, P < 0.0001) and the validation set (N = 80, P < 0.0001) of plasma samples of patients with gastric cancer. The sensitivity was obviously higher than the current biomarkers CEA and CA19-9 (81.25 % vs. 22.54 % and 15.71 %). MiR-940 was also significantly downregulated in gastric cancer tissue samples (N = 34, P = 0.0015), as well as in cancer cell lines (N = 7). Importantly, miR-940 was significantly highly expressed in stomach tissue samples than in other types of tissue samples including the liver, breast, thyroid, and lung. Moreover, there was a trend of lower expression of miR-940 from early to advanced stage of gastric cancer. Target prediction suggested that miR-940 regulated cell signaling including NF-κB and Wnt/β-catenin, as well as pathways of cell communication and adhesion. These pathways play critical roles in gastric cancer initiation and progression. It is the first report that miR-940 may mainly express in the stomach. Downregulation of plasma miR-940 may serve as a novel biomarker for detection of gastric cancer.

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B7-H3 is Overexpressed in Patients Suffering Osteosarcoma and Associated with Tumor Aggressiveness and Metastasis

Cited by 134 publications

References 40 publications

B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity

B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity

Humanized Affinity-matured Monoclonal Antibody 8H9 Has Potent Antitumor Activity and Binds to FG Loop of Tumor Antigen B7-H3

Plasma miR-940 may serve as a novel biomarker for gastric cancer

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