TY - JOUR T1 - Pathological Significance and Prognostic Value of Surfactant Protein D in Cancer. JF - Front Immunol Y1 - 2018 A1 - Mangogna, Alessandro A1 - Belmonte, Beatrice A1 - Agostinis, Chiara A1 - Ricci, Giuseppe A1 - Gulino, Alessandro A1 - Ferrara, Ines A1 - Zanconati, Fabrizio A1 - Tripodo, Claudio A1 - Romano, Federico A1 - Kishore, Uday A1 - Bulla, Roberta AB -

Surfactant protein D (SP-D) is a pattern recognition molecule belonging to the Collectin (collagen-containing C-type lectin) family that has pulmonary as well as extra-pulmonary existence. In the lungs, it is a well-established opsonin that can agglutinate a range of microbes, and enhance their clearance phagocytosis and super-oxidative burst. It can interfere with allergen-IgE interaction and suppress basophil and mast cell activation. However, it is now becoming evident that SP-D is likely to be an innate immune surveillance molecule against tumor development. SP-D has been shown to induce apoptosis in sensitized eosinophils derived from allergic patients and a leukemic cell line p53 pathway. Recently, SP-D has been shown to suppress lung cancer progression interference with the epidermal growth factor signaling. In addition, a truncated form of recombinant human SP-D has been reported to induce apoptosis in pancreatic adenocarcinoma Fas-mediated pathway in a p53-independent manner. To further establish a correlation between SP-D presence/levels and normal and cancer tissues, we performed a bioinformatics analysis, using Oncomine dataset and the survival analysis platforms Kaplan-Meier plotter, to assess if SP-D can serve as a potential prognostic marker for human lung cancer, in addition to human gastric, breast, and ovarian cancers. We also analyzed immunohistochemically the presence of SP-D in normal and tumor human tissues. We conclude that (1) in the lung, gastric, and breast cancers, there is a lower expression of SP-D than normal tissues; (2) in ovarian cancer, there is a higher expression of SP-D than normal tissue; and (3) in lung cancer, the presence of SP-D could be associated with a favorable prognosis. On the contrary, at non-pulmonary sites such as gastric, breast, and ovarian cancers, the presence of SP-D could be associated with unfavorable prognosis. Correlation between the levels of SP-D and overall survival requires further investigation. Our analysis involves a large number of dataset; therefore, any trend observed is reliable. Despite apparent complexity within the results, it is evident that cancer tissues that produce less levels of SP-D compared to their normal tissue counterparts are probably less susceptible to SP-D-mediated immune surveillance mechanisms infiltrating immune cells.

VL - 9 U1 - http://www.ncbi.nlm.nih.gov/pubmed/30127783?dopt=Abstract ER - TY - JOUR T1 - Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth. JF - Front Immunol Y1 - 2017 A1 - Agostinis, Chiara A1 - Vidergar, Romana A1 - Belmonte, Beatrice A1 - Mangogna, Alessandro A1 - Amadio, Leonardo A1 - Geri, Pietro A1 - Borelli, Violetta A1 - Zanconati, Fabrizio A1 - Tedesco, Francesco A1 - Confalonieri, Marco A1 - Tripodo, Claudio A1 - Kishore, Uday A1 - Bulla, Roberta AB -

C1q is the first recognition subcomponent of the complement classical pathway, which acts toward the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, and has been shown to be involved in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumor by encouraging their adhesion, migration, and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of human C1q in the microenvironment of malignant pleural mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM histotypes, particularly in epithelioid rather than in sarcomatoid histotype. C1q avidly bound high and low molecular weight hyaluronic acid (HA) its globular domain. C1q bound to HA was able to induce adhesion and proliferation of mesothelioma cells (MES) enhancement of ERK1/2, SAPK/JNK, and p38 phosphorylation; however, it did not activate the complement cascade. Consistent with the modular organization of the globular domain, we demonstrated that C1q may bind to HA through ghA module, whereas it may interact with human MES through the ghC. In conclusion, C1q highly expressed in MPM binds to HA and enhances the tumor growth promoting cell adhesion and proliferation. These data can help develop novel diagnostic markers and molecular targets for MPM.

VL - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29209316?dopt=Abstract ER -