B7-H3 promotes metastasis, proliferation, and epithelial-mesenchymal transition in lung adenocarcinoma

Yu, Tingting; Zhang, Tao; Lü, Xi; Wang, Ruo-Zheng

doi:10.2147/ott.s169811

Cited by 43 publications

(34 citation statements)

References 20 publications

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“…Downregulation of B7-H3 expression in human lung adenocarcinoma cells can suppress the proliferation, migration, and invasive capacity of cancer cells. 35 Additionally, higher expression of B7-H3 in cervical cancer tissue was reported to be significantly associated with the depth of cancer invasion and poor survival. 15 Silencing or overexpression of B7-H3 in cervical cancer cell lines showed that B7-H3 is involved in cell proliferation and apoptosis of various tumor cells.…”

Section: Discussionmentioning

confidence: 99%

B7-H3 Regulates Glioma Growth and Cell Invasion Through a JAK2/STAT3/Slug-Dependent Signaling Pathway

Zhong¹,

Tao²,

Chen³

et al. 2020

OTT

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The aim of this study was to explore the potential role of B7-H3 in malignant glioma progression and identify an innovative approach in clinical glioma therapy. Methods: The protein expression of B7-H3 in high-and low-grade tumor tissues from glioma patients was assessed by immunohistochemistry. The proliferative and invasive ability of B7-H3-overexpressing or knockout glioma cells was analyzed in vitro and in vivo by CCK-8 assay and an orthotopic mouse glioma model, respectively. Activation of the JAK2/STAT3/Slug signaling pathway and epithelial-mesenchymal transition (EMT) was examined by Western blotting and immunofluorescence. The anticancer effects of napabucasin (NAP) and temozolomide (TMZ) were analyzed in an orthotopic mouse glioma model. Results: The expression of B7-H3 was higher in high-grade than in low-grade tumor tissues from glioma patients. In line with this, overexpression of B7-H3 enhanced glioma cell proliferation, induced sustained glioma growth, and promoted glioma cell invasion in vitro and in vivo. Moreover, these effects were mediated through the activation of the JAK2/ STAT3/Slug signaling pathway in B7-H3 overexpression glioma cells. We also found that B7-H3 induced EMT processes through downregulation of E-cadherin and upregulation of MMP-2/-9 expression, resulting in enhanced invasion of glioma cells. Finally, we show that the combination of NAP and TMZ significantly suppressed glioma growth and glioma cell invasion, both in vitro and in vivo. Conclusion: B7-H3 overexpression facilitated sustained glioma growth and promoted glioma cell invasion through a JAK2/STAT3/Slug-dependent signaling pathway. Application of the STAT3 inhibitor NAP significantly suppressed glioma growth and invasion, and has potential as a therapeutic strategy for the treatment of glioma.

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Section: Discussionmentioning

confidence: 99%

B7-H3 Regulates Glioma Growth and Cell Invasion Through a JAK2/STAT3/Slug-Dependent Signaling Pathway

Zhong¹,

Tao²,

Chen³

et al. 2020

OTT

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“…Accumulating evidence indicated that B7-H3 participates in the metastasis and stemness regulation in some tumor cells. [27][28][29] B7-H3 could facilitate the cancer migration and invasion through the activation of AKT/STAT3 signals in bladder cells. Also, the expression of B7-H3 has been proved to be associated with the sustained cancer cells proliferation and poor prognosis of brain cancer and breast cancer.…”

Section: Discussionmentioning

confidence: 99%

B7-H3 Induces Ovarian Cancer Drugs Resistance Through An PI3K/AKT/BCL-2 Signaling Pathway

Zhou¹,

Zhao²

2019

CMAR

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Purpose: This study was aimed to investigate the underlying mechanism of B7-H3 induced ovarian cancer proliferation and drugs resistance. Materials and methods: We compared the expression of B7-H3 in ovarian tumor tissues from high-malignant or low-malignant patients by immunohistochemistry. We established B7-H3 overexpression and knockout ovarian cells by CRISPR-Cas9 technology and examined the expression of the PI3K/AKT/BCL-2 signals in tumor cells by Western blot or immunofluorescence. We detected the B7-H3 overexpression ovarian cancer cells drugs resistance by CCK8 cell proliferation analysis and Annexin V/PI staining. Tumor-bearing mice were used to investigate the anticancer effects of PI3K/AKT inhibitors in combination with B7-H3 neutralizing antibodies. Results: Enhanced expression of B7-H3 was observed in ovarian tumor tissues from highmalignant patients compared to those from low-malignant patients. Notably, B7-H3 overexpression caused enhanced cells proliferation and chemo-resistance in vitro and in vivo through the activation of PI3K/AKT signaling pathways and up-regulation of BCL-2 protein.Combination of chemotherapeutic agents and B7-H3 neutralizing antibodies efficiently reverses the drugs resistance induced by B7-H3, resulting in improved anticancer effects in ovarian cancer. Conclusion: B7-H3 expression induces the activation the PI3K/AKT signaling pathway and up-regulates BCL-2 in protein level, resulting in the sustained growth and chemo-resistance in ovarian cancer. Blockade of B7-H3 signals efficiently reverses the chemo-resistance, which provides an innovative target in ovarian cancer treatment.

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“…In contrast, numerous studies have unanimously shown that B7-H3 plays a negative role in cancer progression. B7-H3 triggers protumorigenic signals including PI3K/AKT, JAK2/STAT3, and Raf/MEK/ERK1/2 to promote cancer invasion, migration, angiogenesis, drugs sensitivity, and the Warburg effect [ 17 – 24 ]. Thus, B7-H3 may act as a new target for cancer immunotherapy [ 19 – 25 ].…”

Section: Introductionmentioning

confidence: 99%

B7-H3-Induced Signaling in Lung Adenocarcinoma Cell Lines with Divergent Epidermal Growth Factor Receptor Mutation Patterns

Ding

Liao

Zhou

et al. 2020

BioMed Research International

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The cosignal molecule B7-H3 is gaining attention due to its abnormal expression and abundant signal transduction in many types of malignancies. B7-H3-induced signaling includes at least three cascades: PI3K/AKT, JAK2/STAT3, and Raf/MEK/ERK1/2, which are also involved in epidermal growth factor receptor- (EGFR-) triggered signaling in lung adenocarcinoma cells. However, the correlation between B7-H3-induced signaling and EGFR signaling, and between B7-H3-targeted immunotherapy and EGFR-targeted therapy in lung adenocarcinoma, remains to be elucidated. Herein we find that knockout of B7-H3 gene decreased cell survival and increased EGFR-tyrosine kinase inhibitor gefitinib susceptibility of both H3255 and HCC827 cells, two lung adenocarcinoma cell lines harboring EGFR L858R (exon 21) and Del E746-A750 (exon 19) mutations, respectively. B7-H3 deletion resulted in dramatic reduction of phosphorylation level of AKT and STAT3 in H3255 cells while having mild-to-moderate suppression on AKT, STAT3, and ERK1/2 in HCC827 cells. Gefitinib had similar effects with B7-H3 deletion both in H3255 and HCC827 cells. Furthermore, B7-H3 ablation had significant synergistic effects with gefitinib in HCC827 cells. Collectively, our study reveals B7-H3-induced signaling in lung adenocarcinoma cell lines with divergent EGFR mutations, and a translational potential of combined targeted therapy of B7-H3 and EGFR in lung adenocarcinoma with EGFR Del E746-A750 mutation.

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B7-H3 promotes metastasis, proliferation, and epithelial-mesenchymal transition in lung adenocarcinoma

Cited by 43 publications

References 20 publications

<p>B7-H3 Regulates Glioma Growth and Cell Invasion Through a JAK2/STAT3/Slug-Dependent Signaling Pathway</p>

<p>B7-H3 Regulates Glioma Growth and Cell Invasion Through a JAK2/STAT3/Slug-Dependent Signaling Pathway</p>

<p>B7-H3 Induces Ovarian Cancer Drugs Resistance Through An PI3K/AKT/BCL-2 Signaling Pathway</p>

B7-H3-Induced Signaling in Lung Adenocarcinoma Cell Lines with Divergent Epidermal Growth Factor Receptor Mutation Patterns

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