Immunohistochemical analysis of NaPi2b protein (MX35 antigen) expression and subcellular localization in human normal and cancer tissues

Aim: To study the expression profile of the NaPi2b protein and its localization in breast, ovarian and lung cancer cells in relation to normal tissues adjacent to tumor. Methods: Immunohistochemical analysis with monoclonal antibody MX35 was applied for investigation of NaPi2b protein expression in breast, lung and ovarian carcinomas. Intensity of NaPi2b protein expression was calculated with semiquantitative scores. Results: NaPi2b (MX35) protein expression was detected in breast, lung and ovarian cancer cells and adjacent normal tissue. We have shown that in contrast to ovarian tumors in breast and lung tumors NaPi2b expression is down regulated comparing to correspondent normal tissues. Conclusion: This study provides the data on the pattern of NaPi2b expression and cellular localization in breast, lung and ovarian cancers, which might be useful for understanding the mechanism of transport and maintenance of inorganic phosphate in cancer and normal cells, as well as for developing novel immunotherapeutic approaches based on MX35 monoclonal antibody

Is Asthma Related to Choroidal Neovascularization?

BACKGROUND: Age-related degeneration (AMD) and asthma are both diseases that are related to the activation of the complement system. The association between AMD and asthma has been debated in previous studies. The authors investigated the relationship between AMD and asthma systemically. PRINCIPAL FINDINGS: The epidemiological study showed that asthma was related to choroidal neovascularization (CNV) subtype (OR = 1.721, P = 0.023). However, the meta-analysis showed there was no association between AMD and asthma. In an animal model, we found more fluoresce in leakage of CNV lesions by FA analysis and more angiogenesis by histological analysis in rats with asthma. Western blot demonstrated an elevated level of C3α-chain, C3α'-chain and VEGF. After compstatin was intravitreally injected, CNV leakage decreased according to FA analysis, with the level of C3 and VEGF protein decreasing at the same time. SIGNIFICANCE: This study first investigated the relationship between AMD and asthma systematically, and it was found that asthma could be a risk factor for the development of AMD. The study may provide a better understanding of the disease, which may advance the potential for screening asthma patients in clinical practice

Increased levels of the HER1 adaptor protein Ruk(l)/CIN85 contribute to breast cancer malignancy

The adaptor protein regulator for ubiquitous kinase/c-Cbl-interacting protein of 85kDa (Ruk/CIN85) was found to modulate HER1/EGFR signaling and processes like cell adhesion and apoptosis. Although these features imply a role in carcinogenesis, it is so far unknown how and by which molecular mechanisms Ruk/CIN85 could affect a certain tumor phenotype. By analyzing samples from breast cancer patients, we found high levels of Rukl/CIN85 especially in lymph node metastases from patients with invasive breast adenocarcinomas, suggesting that Rukl/CIN85 contributes to malignancy. Expression of Rukl/CIN85 in weakly invasive breast adenocarcinoma cells deficient of Rukl/CIN85 indeed converted them into more malignant cells. In particular, Rukl/CIN85 reduced the growth rate, decreased cell adhesion, enhanced anchorage-independent growth, increased motility in both transwell migration and wound healing assays as well as affected the response to epidermal growth factor. Thereby, Rukl/CIN85 led to a more rapid and prolonged epidermal growth factor-dependent activation of Src, Akt and ERK1/2 and treatment with the Src inhibitor PP2 and the PI3K inhibitor LY294002 abolished the Rukl/CIN85-dependent changes in cell motility. Together, this study indicates that high levels of Rukl/CIN85 contribute to the conversion of breast adenocarcinoma cells into a more malignant phenotype via modulation of the Src/Akt pathway