lactoferrin and Ovarian-Neoplasms

Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin's effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.

Topics: Animals; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic; Cytokines; Disease Models, Animal; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; GPI-Linked Proteins; Humans; Lactoferrin; Lectins; Matrix Metalloproteinase 1; Mice; Neoplasm Invasiveness; Omentum; Ovarian Neoplasms; Ovary; Peritoneal Neoplasms; Recombinant Proteins; Survival Rate; Tumor Microenvironment

LfcinB9 is a peptide derived from lactoferricin B. In the present study, the effect and relative mechanism of LfcinB9 on human ovarian cancer cell line (SK-OV-3) in vitro and in vivo was investigated. The data obtained indicated that LfcinB9 exhibited low hemolysis activity and significantly inhibited the proliferation of SK-OV-3 cells in vitro. In addition, the apoptosis of SK-OV-3 cells was induced through up-regulating the production of reactive oxygen species and activating caspase-3, caspase-9 on both transcription and translation level. Finally, LfcinB9 significantly prevented the tumor growth in the SK-OV-3-bearing mice model. These results indicated that LfcinB9 could be a potential agent for the treatment of ovarian cancer.

Topics: Animals; Antimicrobial Cationic Peptides; Apoptosis; Biomarkers; Cell Line; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Design; Female; Gene Expression Regulation, Neoplastic; Hemolysis; Humans; Injections, Intralesional; Lactoferrin; Mice, Nude; Oligopeptides; Ovarian Neoplasms; Ovary; Peptide Fragments; Random Allocation; Tumor Burden; Xenograft Model Antitumor Assays

Chromosomal DNA sequence polymorphisms may contribute to individuality, confer risk for diseases, and most commonly are used as genetic markers in association study. The iron-binding protein lactoferrin inhibits bacterial growth by sequestering essential iron and also exhibits antitumor, anti-inflammatory, and immunoregulatory activities. The gene coding for lactotransferrin (LTF) is polymorphic, with the occurrence of several common alleles in the general population. This genetically determined variation can affect LTF functions. In this study, we determined the distribution of LTF gene polymorphisms (rs1126477, rs1126478, rs2073495, and rs9110) in the Chinese Han population and investigated whether these polymorphisms were associated with increased risk of ovarian carcinoma in the Chinese. It was found that the rs1126477 was correlated significantly with ovarian cancer. The frequency of A allele of rs1126477 was significantly higher in 700 ovarian cancer patients compared with that in the control group of 700 cases (P< 0.01, χ(2)= 6.79). The frequency of AA genotype was significantly higher in ovarian cancer patients compared with that in the control group (P< 0.05, χ(2)= 6.49). AA genotype is the risk factor of ovarian cancer. The odds ratio (OR) was 2.24 and the 95% confidence interval (CI) was 1.08-4.59, respectively. The 'A-G-C-C' haplotype constructed with rs1126477, rs1126478, rs2073495, and rs9110 was the risk factor to be ovarian cancer. The expression of LTF gene was lower in individuals with 'A-G-C-C' haplotype compared with that in individuals without 'A-G-C-C' haplotype. These findings suggested that rs1126477 could play important roles in ovarian carcinoma physiological processes in the Chinese.

Topics: Adenocarcinoma; Adult; Aged; Asian People; Case-Control Studies; Female; Gene Expression; Genetic Predisposition to Disease; Genetic Variation; Haplotypes; Humans; Lactoferrin; Middle Aged; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Risk Factors