@article {10591, title = {Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth.}, journal = {Front Immunol}, volume = {8}, year = {2017}, month = {2017}, pages = {1559}, abstract = {

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.

}, issn = {1664-3224}, doi = {10.3389/fimmu.2017.01559}, author = {Agostinis, Chiara and Vidergar, Romana and Belmonte, Beatrice and Mangogna, Alessandro and Amadio, Leonardo and Geri, Pietro and Borelli, Violetta and Zanconati, Fabrizio and Tedesco, Francesco and Confalonieri, Marco and Tripodo, Claudio and Kishore, Uday and Bulla, Roberta} } @article {8302, title = {C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation.}, journal = {Nat Commun}, volume = {7}, year = {2016}, month = {2016}, pages = {10346}, abstract = {

Complement C1q is the activator of the classical pathway. However, it is now recognized that C1q can exert functions unrelated to complement activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. Compared with wild-type (WT) or C3- or C5-deficient mice, C1q-deficient (C1qa(-/-)) mice bearing a syngeneic B16 melanoma exhibit a slower tumour growth and prolonged survival. This effect is not attributable to differences in the tumour-infiltrating immune cells. Tumours developing in WT mice display early deposition of C1q, higher vascular density and an increase in the number of lung metastases compared with C1qa(-/-) mice. Bone marrow (BM) chimeras between C1qa(-/-) and WT mice identify non-BM-derived cells as the main local source of C1q that can promote cancer cell adhesion, migration and proliferation. Together these findings support a role for locally synthesized C1q in promoting tumour growth.

}, keywords = {Animals, Apoptosis, Cell Line, Tumor, Cell Movement, Cell Proliferation, Complement Activation, Complement C1q, Complement C3, Complement C5, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Neoplasms}, issn = {2041-1723}, doi = {10.1038/ncomms10346}, author = {Bulla, Roberta and Tripodo, Claudio and Rami, Damiano and Ling, Guang Sheng and Agostinis, Chiara and Guarnotta, Carla and Zorzet, Sonia and Durigutto, Paolo and Botto, Marina and Tedesco, Francesco} } @article {3561, title = {C1q as a unique player in angiogenesis with therapeutic implication in wound healing.}, journal = {Proc Natl Acad Sci U S A}, volume = {111}, year = {2014}, month = {2014 Mar 18}, pages = {4209-14}, abstract = {

We have previously shown that C1q is expressed on endothelial cells (ECs) of newly formed decidual tissue. Here we demonstrate that C1q is deposited in wound-healing skin in the absence of C4 and C3 and that C1q mRNA is locally expressed as revealed by real-time PCR and in situ hybridization. C1q was found to induce permeability of the EC monolayer, to stimulate EC proliferation and migration, and to promote tube formation and sprouting of new vessels in a rat aortic ring assay. Using a murine model of wound healing we observed that vessel formation was defective in C1qa(-/-) mice and was restored to normal after local application of C1q. The mean vessel density of wound-healing tissue and the healed wound area were significantly increased in C1q-treated rats. On the basis of these results we suggest that C1q may represent a valuable therapeutic agent that can be used to treat chronic ulcers or other pathological conditions in which angiogenesis is impaired, such as myocardial ischemia.

}, keywords = {Animals, Cell Proliferation, Complement C1q, DNA Primers, Endothelial Cells, Enzyme-Linked Immunosorbent Assay, Human Umbilical Vein Endothelial Cells, Humans, Immunoblotting, Immunohistochemistry, In Situ Hybridization, Mice, Mice, Inbred C57BL, Mice, Knockout, Neovascularization, Physiologic, Rats, Rats, Wistar, Real-Time Polymerase Chain Reaction, Wound Healing}, issn = {1091-6490}, doi = {10.1073/pnas.1311968111}, author = {Bossi, Fleur and Tripodo, Claudio and Rizzi, Lucia and Bulla, Roberta and Agostinis, Chiara and Guarnotta, Carla and Munaut, Carine and Baldassarre, Gustavo and Papa, Giovanni and Zorzet, Sonia and Ghebrehiwet, Berhane and Ling, Guang Sheng and Botto, Marina and Tedesco, Francesco} }