0000000000273887
AUTHOR
Uday Kishore
Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation
AbstractThe pathophysiology of endometriosis (EM) is an excellent example of immune dysfunction, reminiscent of tumor microenvironment as well. Here, we report that an interplay between C3 and mast cells (MCs) is involved in the pathogenesis of ectopic EM. C3 is at the epicenter of the regulatory feed forward loop, amplifying the inflammatory microenvironment, in which the MCs are protagonists. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse, into the peritoneum of the recipient mice. The wild type mice showed greater amount of…
The Inflammatory Feed-Forward Loop Triggered by the Complement Component C3 as a Potential Target in Endometriosis
Copyright © 2021 Agostinis, Zorzet, Balduit, Zito, Mangogna, Macor, Romano, Toffoli, Belmonte, Morello, Martorana, Borelli, Ricci, Kishore and Bulla. The complement system is a major component of humoral innate immunity, acting as a first line of defense against microbes via opsonization and lysis of pathogens. However, novel roles of the complement system in inflammatory and immunological processes, including in cancer, are emerging. Endometriosis (EM), a benign disease characterized by ectopic endometrial implants, shows certain unique features of cancer, such as the capacity to invade surrounding tissues, and in severe cases, metastatic properties. A defective immune surveillance against…
A longitudinal study of C1q and anti-C1q autoantibodies in homologous and heterologous pregnancies for predicting pre-eclampsia
C1q, the recognition molecule of the classical pathway of the complement system, plays a central role in pregnancy. Lack of C1q is characterized by poor trophoblast invasion and pregnancy failure. C1q can be the target of an antibody response: anti‐C1q autoantibodies (anti-C1q) are present in several infectious and autoimmune diseases. The presence of these autoantibodies has been detected also in 2-8% of the general population. Recent evidence indicates that women who undergo assisted reproductive technology (ART) have an increased risk of developing pre-eclampsia (PE), particularly oocyte donation (OD) pregnancies. The aim of this study was to characterize the levels of C1q and anti-C1q i…
Prognostic Implications of the Complement Protein C1q in Gliomas
The contribution of the complement system in the pathophysiology of brain cancers has been recently considered in light of its well-known involvement in carcinogenesis. Complement system represents an important component of the inflammatory response, which acts as a functional bridge between the innate and adaptive immune response. C1q, the first recognition subcomponent of the complement classical pathway, has recently been shown to be involved in a range of pathophysiological functions that are not dependent on complement activation. C1q is expressed in the microenvironment of various types of human tumors, including melanoma, prostate, mesothelioma, and ovarian cancers, where it can exer…
Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth
C1q is the first recognition subcomponent of the complement classical pathway, which acts towards the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, including their involvement in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumour by encouraging their adhesion, migration and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of C1q in the microenvironment of malignant pleuric mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM…
Pathological significance and prognostic value of surfactant protein D in cancer
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 via 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 via …
Hyaluronic Acid Present in the Tumor Microenvironment Can Negate the Pro-apototic Effect of a Recombinant Fragment of Human Surfactant Protein D on Breast Cancer Cells
Copyright © 2020 Murugaiah, Agostinis, Varghese, Belmonte, Vieni, Alaql, Alrokayan, Khan, Kaur, Roberts, Madan, Bulla and Kishore. Human surfactant protein D (SP-D) belongs to the family of collectins that is composed of a characteristic amino-terminal collagenous region and a carboxy-terminal C-type lectin domain. Being present at the mucosal surfaces, SP-D acts as is a potent innate immune molecule and offers protection against non-self and altered self-such as pathogens, allergens, and tumour. Here, we examined the effect of a recombinant fragment of human SP-D (rfhSP-D) on a range of breast cancer lines. Breast cancer has four molecular subtypes characterised by varied expression of oes…
Prognostic Value of Complement Properdin in Cancer
© 2021 Mangogna, Varghese, Agostinis, Alrokayan, Khan, Stover, Belmonte, Martorana, Ricci, Bulla and Kishore. The complement system is readily triggered by the presence of damage-associated molecular patterns on the surface of tumour cells. The complement alternative pathway provides rapid amplification of the molecular stress signal, leading to complement cascade actvation to deal with pathogens or malignant cells. Properdin is the only known positive regulator of the alternative pathway. In addition, properdin promotes the phagocytic uptake of apoptotic T cells by macrophages and dendritic cells without activating the complement system, thus, establishing its ability to recognize “altered…
Is the Complement Protein C1q a Pro- or Anti-tumorigenic Factor? Bioinformatics Analysis Involving Human Carcinomas
C1q is the first subcomponent of the classical pathway of the complement system and belongs to the C1q/Tumor Necrosis Factor superfamily. C1q can perform a diverse range of immune and non-immune functions in a complement-dependent as well as -independent manner. Being a pattern recognition molecule of the innate immunity, C1q can recognize a number of self, non-self and altered-self ligands and bring about effector mechanisms designed to clear pathogens via opsonisation and inflammatory response. C1q is locally synthesized by macrophages and dendritic cells, and thus, can get involved in a range of biological processes, such as angiogenesis and tissue remodeling, immune modulation, and immu…