TY - JOUR T1 - C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation. JF - Nat Commun Y1 - 2016 A1 - Bulla, Roberta A1 - Tripodo, Claudio A1 - Rami, Damiano A1 - Ling, Guang Sheng A1 - Agostinis, Chiara A1 - Guarnotta, Carla A1 - Zorzet, Sonia A1 - Durigutto, Paolo A1 - Botto, Marina A1 - Tedesco, Francesco KW - Animals KW - Apoptosis KW - Cell Line, Tumor KW - Cell Movement KW - Cell Proliferation KW - Complement Activation KW - Complement C1q KW - Complement C3 KW - Complement C5 KW - Humans KW - Mice KW - Mice, Inbred C57BL KW - Mice, Knockout KW - Neoplasms AB -

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.

VL - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26831747?dopt=Abstract ER - TY - JOUR T1 - Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies. JF - Int J Nanomedicine Y1 - 2015 A1 - Capolla, Sara A1 - Garrovo, Chiara A1 - Zorzet, Sonia A1 - Lorenzon, Andrea A1 - Rampazzo, Enrico A1 - Spretz, Ruben A1 - Pozzato, Gabriele A1 - Núñez, Luis A1 - Tripodo, Claudio A1 - Macor, Paolo A1 - Biffi, Stefania AB -

The expectations of nanoparticle (NP)-based targeted drug delivery systems in cancer, when compared with convectional therapeutic methods, are greater efficacy and reduced drug side effects due to specific cellular-level interactions. However, there are conflicting literature reports on enhanced tumor accumulation of targeted NPs, which is essential for translating their applications as improved drug-delivery systems and contrast agents in cancer imaging. In this study, we characterized biodegradable NPs conjugated with an anti-CD20 antibody for in vivo imaging and drug delivery onto tumor cells. NPs' binding specificity mediated by anti-CD20 antibody was evaluated on MEC1 cells and chronic lymphocytic leukemia patients' cells. The whole-body distribution of untargeted NPs and anti-CD20 NPs were compared by time-domain optical imaging in a localized human/mouse model of B-cell malignancy. These studies provided evidence that NPs' functionalization by an anti-CD20 antibody improves tumor pharmacokinetic profiles in vivo after systemic administration and increases in vivo imaging of tumor mass compared to non-targeted NPs. Together, drug delivery and imaging probe represents a promising theranostics tool for targeting B-cell malignancies.

VL - 10 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26124662?dopt=Abstract ER - TY - JOUR T1 - C1q as a unique player in angiogenesis with therapeutic implication in wound healing. JF - Proc Natl Acad Sci U S A Y1 - 2014 A1 - Bossi, Fleur A1 - Tripodo, Claudio A1 - Rizzi, Lucia A1 - Bulla, Roberta A1 - Agostinis, Chiara A1 - Guarnotta, Carla A1 - Munaut, Carine A1 - Baldassarre, Gustavo A1 - Papa, Giovanni A1 - Zorzet, Sonia A1 - Ghebrehiwet, Berhane A1 - Ling, Guang Sheng A1 - Botto, Marina A1 - Tedesco, Francesco KW - Animals KW - Cell Proliferation KW - Complement C1q KW - DNA Primers KW - Endothelial Cells KW - Enzyme-Linked Immunosorbent Assay KW - Human Umbilical Vein Endothelial Cells KW - Humans KW - Immunoblotting KW - Immunohistochemistry KW - In Situ Hybridization KW - Mice KW - Mice, Inbred C57BL KW - Mice, Knockout KW - Neovascularization, Physiologic KW - Rats KW - Rats, Wistar KW - Real-Time Polymerase Chain Reaction KW - Wound Healing AB -

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.

VL - 111 IS - 11 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24591625?dopt=Abstract ER - TY - JOUR T1 - In vivo anti-lymphoma activity of an agonistic human recombinant anti-TRAIL-R2 minibody. JF - Invest New Drugs Y1 - 2012 A1 - Zauli, Giorgio A1 - Corallini, Federica A1 - Zorzet, Sonia A1 - Grill, Vittorio A1 - Marzari, Roberto A1 - Secchiero, Paola KW - Animals KW - Humans KW - Immunotherapy KW - Injections, Intraperitoneal KW - Lymphoma, B-Cell KW - Mice KW - Mice, SCID KW - Receptors, TNF-Related Apoptosis-Inducing Ligand KW - Single-Chain Antibodies KW - Time Factors KW - Xenograft Model Antitumor Assays AB -

A new single-chain fragment variable (scFv) to TRAIL-R2 receptor produced as minibody (MB2.23) was characterized for anti-lymphoma activity in vivo. For this purpose, a disseminated lymphoma model was generated by intraperitoneal inoculation of BJAB cells in severe combined immunodeficiency mice. Two weekly injections with MB2.23 (10 mg/kg) were able to significantly increase the median survival time of lymphoma-bearing animals with respect to the vehicle-treated control mice, providing a rationale for further investigating the use of MB2.23 in anticancer therapy.

VL - 30 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20714918?dopt=Abstract ER -