Key Role of CD151-integrin Complex in Lung Cancer Metastasis and Mechanisms Involved

Tetraspanin CD151 was found to be upregulated in malignant cell types and has been identified as a tumor metastasis promoter.In this study,we aimed to examine the role of the CD151-integrin complex in lung cancer metastasis and the underlying mechanisms.CD151 QRD194–196→AAA194–196 mutant was generated and used to transfect A549 human lung adenocarcinoma cells.We found that there was no significant difference in CD151 protein expression between CD151 and CD151-AAA mutant groups.In vitro,CD151-AAA mutant delivery abrogated the migration and invasion of A549 cells,which was promoted by CD151 gene transfer.Furthermore,CD151-AAA delivery failed to activate FAK and p130Cas signaling pathways.Western blot and immunohistochemical staining showed strong CD151 expression in lung cancerous tissues but not in adjacent normal tissues.Increased level of CD151 protein was observed in 20 of the patients and the positive rate of CD151 protein in specimens was 62.5%(20/32).In addition,CD151 was co-localized withα3 integrin at the cell-cell contact site in carcinoma tissues.These results suggested that the disruption of the CD151-α3 integrin complex may impair the metastasis-promoting effects and signaling events induced by CD151 in lung cancer.Our findings identified a key role for CD151-α3 integrin complex as a promoter in the lung cancer.

Relationship between Coronary Artery Tortuosity and Cardiorespiratory Fitness in Patients without Obstructed Coronaries

Objective This study aimed to analyze the relationship between cardiorespiratory fitness(CRF)and the increasing severity of coronary artery tortuosity(CAT)in patients with non-stenosed coronaries.Methods A total of 396 patients who underwent coronary angiography and cardiopulmonary exercise testing(CPET)between August 2020 and July 2021 were included in this single-center retrospective study after excluding patients with significant coronary artery disease(≥50%stenosis).Patients were divided into two groups:no or mild coronary artery tortuosity(N/M-CAT)and moderate to severe coronary artery tortuosity(M/S-CAT)and laboratory electrocardiographic,echocardiographic,and CPET parameters were compared between two groups.Results M/S-CAT was found in 46.9%of the study participants,with 66.7%being women.M/S-CAT was significantly associated with advanced age(P=0.014)and females(P=0.001).Diastolic dysfunction parameters,E velocity(P=0.011),and E/A ratio(P=0.004)also revealed significant differences between the M/S-CAT group and N/M-CAT group.VO2@peak(1.22±0.39 vs.1.07±0.39,P<0.01)and VO2@AT(0.77±0.22 vs.0.71±0.21,P=0.017)were significantly lower in the M/S-CAT group than in the N/M-CAT group.Multivariate logistic regression analysis identified females(OR=0.448;95%CI,0.296–0.676;P=0.000)and E/A ratio(OR=0.307;95%CI,0.139–0.680;P=0.004)to be independent risk factors of M/S-CAT and showed no association of CPET parameters to M/S-CAT.Conclusion The results indicate that increasing severity of CAT is strongly associated with female gender and E/A ratio and is not directly correlated with decreasing CRF.Further research with a larger patient population and a longer follow-up time is required to fully comprehend the impact of CAT on CRF.