integrin α2
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Author(s):  
Slavomir Krajnak ◽  
Jörg Jäkel ◽  
Katharina Anić ◽  
Roxana Schwab ◽  
Marcus Schmidt ◽  
...  

Abstract Purpose Integrins may be involved in the metastatic spread of high-grade serous ovarian cancer (HGSOC) which determines the therapeutical approach and prognosis. We investigated the integrin expression in primary tumor and metastases of advanced HGSOC. Methods The expression of integrin α2, α4, α5, α6, and β1 was assessed by immunostaining in tumor samples of the ovary, omentum, and peritoneum of each patient. Differences in integrin expression among tumor localizations and their association with clinicopathological parameters were examined by Fisher’s exact test. The impact of integrin expression on progression-free survival (PFS) and overall survival (OS) was examined by Cox regression and Kaplan–Meier analyses. Results Hundred and thirteen tumor samples of 40 HGSOC patients were examined. The expression of the integrins did not differ between the three tumor localizations (all p values > 0.05) with the exception of high expression of integrin α4 in primary tumor and omentum (52.5% versus 47.5%, p = 0.008) and primary tumor and peritoneum (52.5% versus 47.5%, p = 0.050). High expression of integrin α4 in peritoneum was associated with poorer PFS (HR 2.02 95% CI 1.01–4.05, p = 0.047), younger age (p = 0.047), and death (p = 0.046). Median PFS in patients with high expression of integrin α4 was 13.00 months, whereas median PFS in patients without high expression of integrin α4 was 21.00 months (p = 0.040). Expression of other integrins did not correlate with PFS or OS. Conclusion Expression of integrin α4 may be altered during the metastatic spread of HGSOC and affect prognosis, whereas expression of integrin α2, α5, α6, and β1 did not reveal any prognostic value.


iScience ◽  
2021 ◽  
Vol 24 (10) ◽  
pp. 103168
Author(s):  
Yen-Lin Huang ◽  
Ching-Yeu Liang ◽  
Vera Labitzky ◽  
Danilo Ritz ◽  
Tiago Oliveira ◽  
...  

2021 ◽  
Author(s):  
M Juratli ◽  
E Oppermann ◽  
B Strücker ◽  
A Pascher ◽  
WO Bechstein ◽  
...  
Keyword(s):  

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Michael David Hülskamp ◽  
Daniel Kronenberg ◽  
Richard Stange

Abstract Background The mechanism of small-molecule stabilised protein-protein interactions is of growing interest in the pharmacological discovery process. A plethora of different substances including the aromatic sulphonamide E7820 have been identified to act by such a mechanism. The process of E7820 induced CAPERα degradation and the resultant transcriptional down regulation of integrin α2 expression has previously been described for a variety of different cell lines and been made responsible for E7820’s antiangiogenic activity. Currently the application of E7820 in the treatment of various malignancies including pancreas carcinoma and breast cancer is being investigated in pre-clinical and clinical trials. It has been shown, that integrin α2 deficiency has beneficial effects on bone homeostasis in mice. To transfer E7820 treatment to bone-related pathologies, as non-healing fractures, osteoporosis and bone cancer might therefore be beneficial. However, at present no data is available on the effect of E7820 on osseous cells or skeletal malignancies. Methods Pre-osteoblastic (MC3T3 and Saos-2) cells and endothelial (eEnd2 cells and HUVECs) cells, each of human and murine origin respectively, were investigated. Vitality assay with different concentrations of E7820 were performed. All consecutive experiments were done at a final concentration of 50 ng/ml E7820. The expression and production of integrin α2 and CAPERα were investigated by quantitative real-time PCR and western blotting. Expression of CAPERα splice forms was differentiated by semi-quantitiative reverse transcriptase PCR. Results Here we present the first data showing that E7820 can increase integrin α2 expression in the pre-osteoblast MC3T3 cell line whilst also reproducing canonical E7820 activity in HUVECs. We show that the aberrant activity of E7820 in MC3T3 cells is likely due to differential activity of CAPERα at the integrin α2 promoter, rather than due to differential CAPERα degradation or differential expression of CAPERα spliceforms. Conclusion The results presented here indicate that E7820 may not be suitable to treat certain malignancies of musculoskeletal origin, due to the increase in integrin α2 expression it may induce. Further investigation of the differential functioning of CAPERα and the integrin α2 promoter in cells of various origin would however be necessary to more clearly differentiate between cell lines that will positively respond to E7820 from those that will not.


2021 ◽  
Author(s):  
LingNan He ◽  
WeiJun Wang ◽  
HuiYing Shi ◽  
Chen Jiang ◽  
HaiLing Yao ◽  
...  

Abstract BackgroundBM-MSCs contribute to Helicobacter pylori (H. pylori)-induced gastric cancer, but its mechanism is still unclear. The aim of our study is to investigate the specific role and mechanism of BM-MSCs in H. pylori-induced gastric cancer.Main methodsMice were received total bone marrow transplantations and then infected with H. pylori. BM-MSCs were extracted and transplanted to gastric serosal layer of mice infected with H. pylori chronically. Hematoxylin and eosin staining, immunohistochemistry staining and immunofluorescence were performed to detect the tumor growth and angiogenesis in mice stomach tissues. Chicken chorioallantoic membrane assay, xenograft tumor model, and Human umbilical vein endothelial cells tube formation assay were used for in vivo and in vitro angiogenesis study. THBS4 was screened out from RNA-SEQ Analysis with gastric tissues of BM-MSCs transplantation into H. pylori infected mice.ResultsBM-MSCs can migrate to the site of chronic mucosal injury and promote tumor angiogenesis associated with chronic H. pylori infection. Migration of BM-MSCs to the site of chronic mucosal injury induced the up-regulation of THBS4, which was evident also in human gastric cancer, and correlated with more blood vessel formation and worse outcome. THBS4/Integrin α2 axis exhibited promoting angiogenesis by facilitating PI3K/AKT pathway in endothelial cells.ConclusionsOur results discover that BM-MSCs have a new pro-angiogenic effect in chronic H. pylori infection microenvironment, primarily through THBS4/Integrin α2 axis, which activated PI3K/AKT pathway in endothelial cells and eventually induced formation of new tumor vessels.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jia Yuan ◽  
Zhiyong Jiang ◽  
Meiai Li ◽  
Wei Li ◽  
Xueping Gu ◽  
...  

Abstract Background Kawasaki disease (KD) is a systemic vasculitis, and the formation of coronary artery lesions(CAL) is its most common sequela. Both genetic and environmental factors are considered to be important factors of in KD. Integrin α2 (ITGA2) is a transmembrane receptor that is associated with susceptibility to several diseases, but its relevance to KD with CAL is unclear. Methods We genotyped ITGA2 rs1126643 in 785 KD patients with the CAL and no-CAL(NCAL) (300 patients with CAL, and 485 age- and sex-matched patients with NCAL). OR (95% CI) and adjusted OR (95% CI) were used to evaluate the intensity of the association. Results We found a significantly increased risk of KD with CAL associated with ITGA2 rs1126643 genotypes (CT vs CC: adjusted OR = 1.57, 95% CI = 1.16–2.12, P = 0.0032; CT/TT vs CC: adjusted OR = 1.49, 95% CI = 1.12–2.00, P = 0.0068; T vs C: adjusted OR = 1.66, 95% CI = 1.16–2.51, P = 0.0165). Moreover, we found that carriers of the CT/TT genotype had a significant risk of KD with coronary artery lesion susceptibility for children ≤60 months of age, and the CT/TT genotype was significantly associated with an increased risk of SCAL formation and MCAL formation when compared with the CC genotype. Conclusion ITGA2 rs1126643 was associated with increased susceptibility and severity of CAL in KD.


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