BackgroundEndometriosis, which shares certain characteristics with cancers, may cause abnormal expression of proteins involved in cell migration. Endometrial epithelial cells (EECs) are believed to play an important role in endometriotic migration. The aim of this study was to investigate the relationship between the expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in endometriotic migration.MethodsWe performed primary culture of EECs and investigated the expression of OPN and MMP-9 in EECs regulated by 17beta-estradiol (E2). OPN-specific siRNA interference was used to down-regulate OPN and to explore the corresponding change in MMP-9 expression. Real-time RT-PCR, western blot analysis and flow cytometry were used to determine the expression levels of OPN and MMP-9. Gelatin zymography was performed to observe the enzymatic activity of MMP-9 in conditioned media. Transwell and wound scratch assays were performed to investigate the migration ability of EECs.ResultsThe expression levels of OPN and MMP-9 in normal EECs (NEECs) were inferior to those in EECs from patients with endometriosis (EEECs). The expression levels of OPN and MMP-9 from stage III/IV EEECs and secretory-phase EECs were higher than those of stage I/II EEECs or proliferative-phase EECs. The expression levels of OPN and MMP-9 in EEECs were increased by E2 treatment and remarkably decreased by siRNA interference. Active MMP-9 expression increased with E2 treatment and decreased with siRNA treatment in EEECs compared with the same treatments in NEECs. The migratory abilities of EEECs were enhanced after cells were treated with E2; in contrast, these abilities were reduced by siRNA interference. In NEECs, active MMP-9 and cellular migration abilities were only minimally influenced by E2 and siRNA treatment.ConclusionsThe present study suggests that the up-regulation of MMP-9 via activation of OPN induced by estrogen may correlate with the migration of endometrial epithelial cells in patients with endometriosis.

Lung cancer is one of the leading malignancies worldwide, but the regulatory mechanism of its growth and metastasis is still poorly understood. We investigated the possible expression of immunoglobulin G (IgG) genes in squamous cell carcinomas and adenocarcinomas of the lung and related cancer cell lines. Abundant mRNA of IgG and essential enzymes for IgG synthesis, recombination activation genes 1, 2 (RAG1, 2) and activation-induced cytidine deaminase (AID) were detected in the cancer cells but not in adjacent normal lung tissue or normal lung epithelial cell line. The extents of IgG expression in 86 lung cancers were found to associate with clinical stage, pathological grade and lymph node metastasis. We found that knockdown of IgG with siRNA resulted in decreases of cellular proliferation, migration and attachment for cultured lung cancer cells. Metastasis-associated gene 1 (MTA1) appeared to be co-expressed with IgG in lung cancer cells. Statistical analysis showed that the rate of IgG expression was significantly correlated to that of MTA1 and to lymph node metastases. Inhibition of MTA1 gene expression with siRNA also led to decreases of cellular migration and attachment for cultured lung cancer cells. These evidences suggested that inhibition of cancer migration and attachment induced by IgG down-regulation might be achieved through MTA1 regulatory pathway. Our findings suggest that lung cancer-produced IgG is likely to play an important role in cancer growth and metastasis with significant clinical implications.

Background Human papillomavirus (HPV) infection is associated with multiple types of cancer, but the evidence has not yet been fully elucidated in bladder cancer. Methods Frozen tissue samples collected from 146 patients aged 32 to 89 years-old with bladder cancer pathological diagnosis between 2015 and 2019 were analyzed. HPV genotyping and integration status determination were performed by capture-based next generation sequencing. Statistical analysis of HPV type distributions was performed according to stage, grade, gender and age group of patients. Results Mean age of 146 patients was 66.64 ± 10.06 years and 83.56% were male. Overall HPV infection rate was 28.77% (37.5% in female and 27% in male), with 11.90% HPV integration events. Among them, 17.12% single and 11.65% co-infections were observed. HPV18 (24.66%) was the most prevalent genotype, followed by HPV33, 16, 39. All HPV were European lineage (A). HPV16 was more prevalent in female (p=0.04). Conclusion HPV infection may contribute a causative role both in men and women with bladder cancer. HPV18, followed by HPV 33, 16 and 39 genotypes potentially represent the predominant oncogenic risk types of bladder carcinogenesis.

Background: Evidence suggested that vaginal microbiome played a functional role in the progression of cervical lesions in female infected by HPV. This study aimed at evaluating the influence of common vaginal infection on the carcinogenicity of high risk HPV (hr-HPV). Methods: From January 15, 2017 to December 31, 2017, 310,545 female aged at least 30 years old had been recruited for cervical cancer screening from 9 clinical research centers in Central China. All the recruited participants received hr-HPV genotyping for cervical cancer screening and vaginal microenvironment test by a high vaginal swab. Colposcopy-directed biopsy was recommended for female who were infected with HPV 16 and HPV 18, and other positive hr-HPV types through test had undertaken triage using liquid-based cytology, cases with the results ≥ ASCUS among them were referred to colposcopy directly, and cervical tissues were taken for pathology examination to make clear the presence or absence of other cervical lesions. Results: Among 310,545 female, 6067 (1.95%) were tested with positive HPV 16 and HPV 18, 18,297 (5.89%) were tested with other positive hr-HPV genotypes, cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3 and invasive cervical cancer (ICC) were detected in 861 cases, 377 cases, 423 cases, and 77 cases, respectively. Candida albicans and Gardnerella were not associated with the detection of cervical lesions. Positive trichomonas vaginitis (TV) was correlated with hr-HPV infection (p < 0.0001). Co-infection with TV increased the risk of CIN 1 among female infected with hr-HPV (OR 1.18, 95% CI: 1.42-2.31). Co-infection with TV increased the risk of CIN 2-3 among female infected with HPV 16 (OR 1.71, 95% CI: 1.16-2.53). Conclusions: Co-infection of TV and HPV 16 is a significant factor for the detection of cervical lesions.

(1) Immunoglobulin G was locally produced by PC cells and adjacent islet cells. (2) Immunoglobulin G may promote tumor growth by inhibiting cancer cell apoptosis. (3) Locally produced IgG might play a role in PC-associated diabetes.

Recently immunoglobulin G (IgG) was found to be produced by neoplasms and promote tumor growth in cancer cell lines and animal models. To investigate the pathophysiological significance of cancer-produced IgG in breast cancer, we examined the expressions of IgG in 68 breast cancers including 40 primary cancers without metastasis and 28 cancers with axillary lymph node metastases. IgG gene expression was detected in all these samples. We found that IgG-expressing cancer cells were predominantly located in the periphery of the primary cancer nest and that these cells showed more cellular atypia and nuclear pleomorphism. We also found that the abundance of IgG-expressing cancer cells was higher and the cells were more evenly distributed in the metastatic cancer cells than that in the primary lesion. These findings suggest that IgG-expressing breast cancer cells have a more aggressive biological behavior than the IgG negative cancer cells and it could be an indicator for progression and metastasis of the disease. Co-localization of IgG and C1q complement was detected in both primary and metastatic lesions implying that immune complexes might be formed in situ. We speculate that such immune complexes might facilitate immune escape of cancer cells. Our findings suggest that locally produced IgG plays important roles in breast cancer, and may serve as a potential therapeutic target.

Background Endometriosis cause decreases in life quality and pelvic pain in reproductive-age women. Methylation abnormalities played a functional role in the progression of endometriosis, this study aimed to explore the mechanisms mediated by abnormal methylation in the development of EMS. Materials and methods Next-generation sequencing dataset and methylation profiling dataset were used to screen out the key gene SFRP2. Western bolt, Real-time PCR, Aza-2?deoxycytidine treatment, luciferase reporter assay, Methylation-specific PCR , Bisulfite sequencing PCR and lentivirus infection were carried out to detect the methylation status and signaling pathway with the primary epithelial cells. Transwell assay and wound scratch assay were implemented to observe the differences of migration ability with the intervening with the expression of SFRP2. Results To define the role of the DNA methylation-regulated genes in the pathogenesis of EMS, we performed both DNA methylomic and expression analyses of ectopic endometrium and ectopic endometrium epithelial cells(EEECs) and found that SFRP2 is demethylated/upregulated in ectopic endometrium and EEECs. The expression of lentivirus carrying SFRP2 cDNA up-regulates the activity of Wnt signaling and the protein expression of ?-catenin in EEECs. SFRP2 impact on the invasion and migration of ectopic endometrium by modulating the activities of the Wnt/?-catenin signaling pathway. The invasion and migration ability of EEECs were significantly strengthened after demethylation treatment including 5-Aza and the knockdown of DNMT1. Conclusion In summary, the increased SFRP2 expression-induced Wnt/?-catenin signaling due to the demethylation of the SFRP2 promoter plays an important role in the pathogenesis of EMS, suggesting that SFRP2 might be a therapeutic target for EMS treatment.

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