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

Zhang, Wei; Wang, Yanfang; Wang, Jing; Dong, Fang; Zhu, Mingxia; Wan, Wenli; Li, Haishen; Wu, Feifei; Yan, Xinxing; Ke, Xiaoyan

doi:10.3892/ijo.2015.2962

Cited by 27 publications

(22 citation statements)

References 34 publications

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“…The same phenomenon was observed in the cell invasion test. Silencing B7-H3 can impede cell migration and inhibit cell invasion via downregulating the expression of MMP-2 (13). Thus, we measured the invasion related proteins by western blotting and found that MMP-2 were lower in A2780-sh-B7-H3 and SKOV3-sh-B7-H3 cells than in the NC groups ( Fig.…”

Section: B7-h3 Expression In Relation To Patient Clinicopathologicalmentioning

confidence: 86%

B7-H3 is related to tumor progression in ovarian cancer

et al. 2017

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B7-H3, a co-stimulatory molecule, has been found expressed in ovarian cancer, but its role and mechanism is not clear. In this study, we further verified the expression of B7-H3 in ovarian carcinoma and normal epithelial ovarian tissues. Three ovarian cancer cell lines, A2780, SKOV3 and HO8910 were selected to explore the effects of B7-H3 on proliferation, apoptosis, migration and invasion. We found that B7-H3 was mainly located in the cytoplasm of ovarian cancer cells as determined by immunofluorescence staining. The ability of cell invasion, migration, proliferation decreased after silencing B7-H3 whereas the apoptosis increased, which was related to the upregulation of Bax, caspase-8, cleaved caspase-8 and the downregulation of Bcl-2, Bcl-xl, matrix metalloproteinase-2 (MMP2) by western blotting. In addition, B7-H3 enhanced the H08910 cell capacities in invasion, migration and proliferation. Expression of the phosphorylation signal transducer and activator of transcription 3 (pStat3) molecules and their upstream molecules phosphorylation Janus kinase 2 (pJak2) were significantly increased. In order to investigate whether B7-H3 plays a role in this pathway, we treated the overexpressed HO8910 cells with AG490 (inhibitors of Jak2). Our findings revealed that B7-H3 affect ovarian cancer progression through the Jak2/Stat3 pathway, indicating that B7-H3 has the potential to be a useful prognostic marker.

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Section: B7-h3 Expression In Relation To Patient Clinicopathologicalmentioning

confidence: 86%

B7-H3 is related to tumor progression in ovarian cancer

et al. 2017

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“…And restoration of CD276 completely abrogated the tumor suppressor role of miR-187. The oncogenic activities of CD276 have been reported in many human cancers, including acute monocytic leukemia [30], non-small cell lung cancer [31], gastrointestinal carcinoma [15, 20, 32], and mantle cell lymphoma [33]. Despite the majority of studies on CD276 and cancer emphasize the paradox immunological role of CD276, several studies showed that CD276 can regulate tumor progression and chemosensitivity by targeting with signaling pathways involved in non-immunological systems.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-187 inhibits tumor growth and invasion by directly targeting CD276 in colorectal cancer

et al. 2016

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Aberrantly expressed microRNAs contribute to the initiation and progression of human cancers. However, the underlying functions of microRNA-187 (miR-187) in colorectal cancer (CRC) remain largely unexplored. Here, we demonstrated that miR-187 was significantly down-regulated in CRC tissues and cell lines compared to their normal counterparts. By Kaplan-Meier analysis, we revealed that decreased miR-187 expression was closely associated with shorter overall survival and relapse-free survival of patients with CRC. By gain- and loss-of-function studies, we showed that miR-187 remarkably suppressed CRC cell proliferation, migration, invasion, and promoted cell apoptosis. Furthermore, bioinformatics analysis and luciferase reporter assay identified that CD276 was the direct functional target of miR-187 in CRC. Genetic silencing of CD276 recapitulated similar phenotype as observed in over-expression of miR-187, and restoration of CD276 completely rescued the inhibitory effect of miR-187 in CRC cells. Taken together, our study implied the essential roles of miR-187 in suppressing CRC progression, and a novel link between miR-187 and CD276 in CRC.

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“…Moreover, we found in another study that the treatment using the same plasmid of B7-H3 shRNA combined with other chemotherapy drugs dramatically inhibited the growth of mantle cell lymphoma Maver and Z138 xenografts by 92.3% and 92.9%, respectively. 27 Similarly, previous studies have also reported that B7-H3 may promote cancer resistance to drug treatments in breast cancer and pancreatic carcinoma xenograft models. 28,37 Although B7-H3 is a type I transmembrane protein, we find that its protein is also highly expressed in the nuclei and cytoplasm of AML M5 U937 cells, with a similar subcellular distribution as colorectal cancer, detected by immunohistochemical analysis.…”

Section: Figurementioning

confidence: 78%

“…In order to rule out unspecific effects, we used the same recombinant lentivirus-mediated B7-H3 knockdown in mantle cell lymphoma Maver and Z138 cell lines in another study, and also made the conclusion that B7-H3 promotes mantle cell lymphoma progression and that targeting B7-H3 knockdown significantly enhances the chemosensitivity in vitro and in vivo. 27 This indicates that B7-H3 promotes tumor progression in a series of hematologic malignancies, and that B7-H3 silencing enhances chemosensitivity, though not only in U937 cells. The strategy of targeting B7-H3 may provide a new therapeutic approach to hematologic malignancies, such as in AML M5.…”

Section: Resultsmentioning

confidence: 97%

“…Moreover, another in vitro experiment by our research team showed that B7-H3 knockdown decreased the growth of mantle cell lymphoma Maver and Z138 cells by 41.7% and 37.5%, and declined the CFA by 71.2% and 77.2%, respectively. 27 The different effects of B7-H3 may depend on the various tumor types. Then, we established xenograft models to study the in vivo effect of B7-H3 knockdown on tumor growth.…”

Section: Discussionmentioning

confidence: 99%

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B7-H3 Silencing By RNAi Inhibits Tumor Progression and Enhances Chemosensitivity in U937 Cells

Zhang

Wang

et al. 2015

Blood

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Background : Aberrant expression of the immunoregulatory protein B7-H3 in B7 family has been associated with more advanced disease and poor prognosis in a wide range of cancer. However, the role of B7-H3 in acute monocytic leukemia U937 cells has not been thoroughly investigated. In this study, we examined the gene expression and subcellular localization of B7-H3 in human peripheral blood cells and hematologic malignancy cell lines. Then, we determined the effects of down-regulating B7-H3 expression on U937 cells, which has the highest B7-H3 protein expression in the detected cell lines. Methods : B7-H3 expression in 12 healthy volunteer peripheral blood cell samples and 13 human hematologic malignancy cell lines was determined by RT-PCR, western blot and flow cytometry. B7-H3 knockdown in the U937 cell line was performed using shRNA lentivirus transduction. The effects 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. U937 xenograft models were used to assess the effects of B7-H3 on tumorigenicity and Ki-67 and PCNA was detected through immunohistochemical. Changes in cell growth inhibition and apoptosis, when combined with chemotherapy drugs, were determined using CCK-8, Annexin V-FITC/PI and Hoechst 33342 staining assays in vitro. The therapeutic effect of B7-H3 knockdown in combination with chemotherapy drugs were also studied by U937 xenograft models in vivo. Results: B7-H3 mRNA was widely expressed in the 12 hematologic malignancy cell lines except for CZ1 and PB MNCs of volunteers. But the protein level of B7-H3 was only abnormally overexpressed in 12 hematologic malignancy cell lines except for CZ1, with subcellular localizations in nucleus and cytoplasm mostly determined. The down-regulation of B7-H3 in U937 cells significantly decreased cell growth and the rate of colony formation by 32.8% in 72 h and 70.3% in 14 d. Mean inhibition rate of tumor growth with B7-H3 knockdown was 59.4%, and expression of both Ki-67 and PCNA in xenografts was significantly reduced. After B7-H3 silencing, U937 cell cycle was arrested at G0/G1 phase, and the cell cycle-related proteins Cyclin D1 and CDK4 were lower. Cell migration rate of B7-H3 knockdown cells was reduced more than five-fold, and invasion capacity was decreased by 86.7%. The rates of distant metastasis in B7-H3 knockdown xenografts were significantly decreased. The invasion-related proteins MMP-2 and MMP-9 were lower in both B7-H3 knockdown cells and xenografts. B7-H3 RNAi profoundly increased the anti-tumor effect of chemotherapy and enhanced the activity of caspase-3 in vitro and in vivo. At the end of observation (on day 19 after inoculation), inhibition rates of tumor growth in B7-H3 shRNA combined with idarubicin, cytarabine, and idarubicin plus cytarabine groups were 70.5%, 80.0%, and 90.0%, respectively (P=0.006, 0.004 and 0.016). The TUNEL positive cells were significantly increased in the B7-H3 shRNA combined with chemotherapy drugs groups. Conclusions: B7-H3 protein was abnormally overexpressed in 12 hematologic malignancy cell lines except for CZ1, with subcellular localizations in nucleus and cytoplasm mostly determined. B7-H3 may promote U937 cell progression, and shRNA targeting B7-H3 significantly enhances sensitivity to chemotherapeutic drugs. These results may provide new insight into the function of B7-H3 and a promising therapeutic approach targeting B7-H3 in acute monocytic leukemia. Disclosures No relevant conflicts of interest to declare.

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

Cited by 27 publications

References 34 publications

B7-H3 is related to tumor progression in ovarian cancer

B7-H3 is related to tumor progression in ovarian cancer

MicroRNA-187 inhibits tumor growth and invasion by directly targeting CD276 in colorectal cancer

B7-H3 Silencing By RNAi Inhibits Tumor Progression and Enhances Chemosensitivity in U937 Cells

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