C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation

Nature Communications

Volumn 7, Issue , 2016, Pages

  Bulla, Roberta ^a   Tripodo, Claudio ^b   Rami, Damiano ^a   Ling, Guang Sheng ^c   Agostinis, Chiara ^d   Guarnotta, Carla ^b   Zorzet, Sonia ^a   Durigutto, Paolo ^a   Botto, Marina ^c   Tedesco, Francesco ^e  

^a UNIVERSITY OF TRIESTE   (Italy)

^b UNIVERSITY OF PALERMO   (Italy)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

^d INSTITUTE FOR MATERNAL AND CHILD HEALTH IRCCS BURLO GAROFOLO   (Italy)

^e ISTITUTO AUXOLOGICO ITALIANO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENT COMPONENT C1Q; COMPLEMENT COMPONENT C3; COMPLEMENT COMPONENT C5;

BONE; CANCER; CELLS AND CELL COMPONENTS; GENE EXPRESSION; PROTEIN; TUMOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER GROWTH; CANCER SURVIVAL; CELL ADHESION; CELL MIGRATION; CELL PROLIFERATION; CHIMERA; COMPLEMENT ACTIVATION; COMPLEMENT DEPOSITION; CONTROLLED STUDY; FEMALE; IMMUNOCOMPETENT CELL; LUNG METASTASIS; MALE; MALIGNANT NEOPLASTIC DISEASE; MELANOMA B16; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; STROMA; TUMOR MICROENVIRONMENT; TUMOR PROMOTION; VASCULAR ENDOTHELIUM; ANIMAL; APOPTOSIS; C57BL MOUSE; CELL MOTION; GENETICS; HUMAN; KNOCKOUT MOUSE; METABOLISM; NEOPLASM; PHYSIOLOGY; TUMOR CELL LINE;

MUS;

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;

EID: 84956640309     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms10346     Document Type: Article

References (66)

1. Hanahan, D., Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646-674 (2011).
2. Barcellos-Hoff, M. H., Lyden, D., Wang, T. C. The evolution of the cancer niche during multistage carcinogenesis. Nat. Rev. Cancer 13, 511-518 (2013).
3. McAllister, S. S., Weinberg, R. A. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat. Cell Biol. 16, 717-727 (2014).
4. Grivennikov, S. I., Greten, F. R., Karin, M. Immunity, inflammation, and cancer. Cell 140, 883-899 (2010).
5. Schreiber, R. D., Old, L. J., Smyth, M. J. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331, 1565-1570 (2011).
6. Aguirre-Ghiso, J. A. Models, mechanisms and clinical evidence for cancer dormancy. Nat. Rev. Cancer. 7, 834-846 (2007).
7. Welch, H. G., Black, W. C. Overdiagnosis in cancer. J. Natl. Cancer Inst. 102, 605-613 (2010).
8. Sosa, M. S., Bragado, P., Aguirre-Ghiso, J. A. Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat. Rev. Cancer 14, 611-622 (2014).
9. Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J., Schreiber, R. D. Cancer immunoediting: from immunosurveillance to tumor escape. Nat. Immunol. 3, 991-998 (2002).
10. Steer, H. J., Lake, R. A., Nowak, A. K., Robinson, B. W. S. Harnessing the immune response to treat cancer. Oncogene 29, 6301-6313 (2010).
11. Mittal, D., Gubin, M. M., Schreiber, R. D., Smyth, M. J. New insights into cancer immunoediting and its three component phases-elimination, equilibrium and escape. Curr. Opin. Immunol. 27, 16-25 (2014).
12. Mantovani, A. et al. Cancer-related inflammation. Nature 454, 436-444 (2008).
13. Coussens, L. M., Zitvogel, L., Palucka, A. K. Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science 339, 286-291 (2013).
14. Di Minin, G. et al. Mutant p53 reprograms TNF signaling in cancer cells through interaction with the tumor suppressor DAB2IP. Mol. Cell 56, 617-629 (2014).
15. Hanahan, D., Coussens, L. M. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21, 309-322 (2012).
16. Ricklin, D., Hajishengallis, G., Yang, K., Lambris, J. D. Complement: a key system for immune surveillance and homeostasis. Nat. Immunol. 11, 785-797 (2010).
17. Merle, N. S., Noe, R., Halbwachs-Mecarelli, L., Fremeaux-Bacchi, V., Roumenina, L. T. Complement system part II: role in immunity. Front. Immunol. 6, 257 (2015).
18. Stover, C. Dual role of complement in tumour growth and metastasis (Review). Int. J. Mol. Med. 25, 307-313 (2010).
19. Pio, R., Corrales, L., Lambris, J. D. The role of complement in tumor growth. Adv. Exp. Med. Biol. 772, 229-262 (2014).
20. Markiewski, M. M., Lambris, J. D. Is complement good or bad for cancer patients? A new perspective on an old dilemma. Trends Immunol. 30, 286-292 (2009).
21. Scott, A. M., Wolchok, J. D., Old, L. J. Antibody therapy of cancer. Nat. Rev. Cancer 12, 278-287 (2012).
22. Markiewski, M. M., Lambris, J. D. Unwelcome complement. Cancer Res. 69, 6367-6370 (2009).
23. Meyer, S., Leusen, J. H., Boross, P. Regulation of complement and modulation of its activity in monoclonal antibody therapy of cancer. MAbs 6, 1133-1144 (2014).
24. Taylor, R. P., Lindorfer, M. A. The role of complement in mAb-based therapies of cancer. Methods 65, 18-27 (2014).
25. Melis, J. P. M. et al. Complement in therapy and disease: regulating the complement system with antibody-based therapeutics. Mol. Immunol. 67, 117-130 (2015).
26. Macor, P. et al. Complement activated by chimeric anti-folate receptor antibodies is an efficient effector system to control ovarian carcinoma. Cancer Res. 66, 3876-3883 (2006).
27. Macor, P., Tedesco, F. Complement as effector system in cancer immunotherapy. Immunol. Lett. 111, 6-13 (2007).
28. Macor, P. et al. Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherapy in mice. Leukemia 29, 406-414 (2015).
29. Loveland, B. E., Cebon, J. Cancer exploiting complement: a clue or an exception? Nat. Immunol. 9, 1205-1206 (2008).
30. Markiewski, M. M. et al. Modulation of the antitumor immune response by complement. Nat. Immunol. 9, 1225-1235 (2008).
31. Corrales, L. et al. Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression. J. Immunol. 189, 4674-4683 (2012).
32. Nunez-Cruz, S. et al. Genetic and pharmacologic inhibition of complement impairs endothelial cell function and ablates ovarian cancer neovascularization. Neoplasia 14, 994-1004 (2012).
33. Bonavita, E. et al. PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer. Cell 160, 700-714 (2015).
34. Kim, D.-Y., Martin, C. B., Lee, S. N., Martin, B. K. Expression of complement protein C5a in a murine mammary cancer model: tumor regression by interference with the cell cycle. Cancer Immunol. Immunother. 54, 1026-1037 (2005).
35. Surace, L. et al. Complement is a central mediator of radiotherapy-induced tumor-specific immunity and clinical response. Immunity 42, 767-777 (2015).
36. Gunn, L. et al. Opposing roles for complement component C5a in tumor progression and the tumor microenvironment. J. Immunol. 189, 2985-2994 (2012).
37. Sayegh, E. T., Bloch, O., Parsa, A. T. Complement anaphylatoxins as immune regulators in cancer. Cancer Med. 3, 747-758 (2014).
38. Cho, M. S. et al. Autocrine effects of tumor-derived complement. Cell Rep. 6, 1085-1095 (2014).
39. Agostinis, C. et al. An alternative role of C1q in cell migration and tissue remodeling: contribution to trophoblast invasion and placental development. J. Immunol. 185, 4420-4429 (2010).
40. Bossi, F. et al. C1q as a unique player in angiogenesis with therapeutic implication in wound healing. Proc. Natl Acad. Sci. USA 111, 10-15 (2014).
41. Petry, F., Botto, M., Holtappels, R., Walport, M. J., Loos, M. Reconstitution of the complement function in C1q-deficient (C1qa-/-) mice with wild-type bone marrow cells. J. Immunol. 167, 4033-4037 (2001).
42. Cortes-Hernandez, J. et al. Restoration of C1q levels by bone marrow transplantation attenuates autoimmune disease associated with C1q deficiency in mice. Eur. J. Immunol. 34, 3713-3722 (2004).
43. Carmeliet, P. Angiogenesis in life, disease and medicine. Nature 438, 932-936 (2005).
44. Carmeliet, P., Jain, R. K. Molecular mechanisms and clinical applications of angiogenesis. Nature 473, 298-307 (2011).
45. Potente, M., Gerhardt, H., Carmeliet, P. Basic and therapeutic aspects of angiogenesis. Cell 146, 873-887 (2011).
46. Swartz, M. A. et al. Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Res. 72, 2473-2480 (2012).
47. Junttila, M. R., de Sauvage, F. J. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501, 346-354 (2013).
48. Vlaicu, S. I. et al. Role of C5b-9 complement complex and response gene to complement-32 (RGC-32) in cancer. Immunol. Res. 56, 109-121 (2013).
49. Bulla, R. et al. Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium. Mol. Immunol. 45, 2629-2640 (2008).
50. Nayak, A., Ferluga, J., Tsolaki, A. G., Kishore, U. The non-classical functions of the classical complement pathway recognition subcomponent C1q. Immunol. Lett. 131, 139-150 (2010).
51. Nayak, A., Pednekar, L., Reid, K. B., Kishore, U. Complement and non-complement activating functions of C1q: a prototypical innate immune molecule. Innate Immun. 18, 350-363 (2012).
52. Ghebrehiwet, B., Hosszu, K. K., Valentino, A., Peerschke, E. I. B. The C1q family of proteins: insights into the emerging non-traditional functions. Front. Immunol. 3, 1-9 (2012).
53. Kouser, L. et al. Emerging and novel functions of complement protein C1q. Front. Immunol. 6, 317 (2015).
54. Veerhuis, R., Nielsen, H. M., Tenner, A. J. Complement in the brain. Mol. Immunol. 48, 1592-1603 (2011).
55. Stephan, A. H. et al. A dramatic increase of C1q protein in the CNS during normal aging. J. Neurosci. 33, 13460-13474 (2013).
56. Bulla, R., Bossi, F., Tedesco, F. The complement system at the embryo implantation site: friend or foe? Front. Immunol. 3, 55 (2012).
57. Rutkowski, M. J., Sughrue, M. E., Kane, A. J., Mills, S. A., Parsa, A. T. Cancer and the complement cascade. Mol. Cancer Res. 8, 1453-1465 (2010).
58. Emmett, M. S., Dewing, D., Pritchard-Jones, R. O. Angiogenesis and melanoma-from basic science to clinical trials. Am. J. Cancer Res. 1, 852-868 (2011).
59. Braeuer, R. R. et al. Why is melanoma so metastatic? Pigment Cell Melanoma Res. 27, 19-36 (2014).
60. Dembitzer, F. R. et al. gC1qR expression in normal and pathologic human tissues: differential expression in tissues of epithelial and mesenchymal origin. J. Histochem. Cytochem. 60, 467-474 (2012).
61. Winslow, S., Leandersson, K., Edsjo?, A., Larsson, C. Prognostic stromal gene signatures in breast cancer. Breast Cancer Res. 17, 23 (2015).
62. Wetsel, R. A., Fleischer, D. T., Haviland, D. L. Deficiency of the murine fifth complement component (C5). A 2-base pair gene deletion in a 5'-exon. J. Biol. Chem. 265, 2435-2440 (1990).
63. Wessels, M. R. et al. Studies of group B streptococcal infection in mice deficient in complement component C3 or C4 demonstrate an essential role for complement in both innate and acquired immunity. Proc. Natl Acad. Sci. USA 92, 11490-11494 (1995).
64. Botto, M. et al. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat. Genet. 19, 56-59 (1998).
65. Gava, B., Zorzet, S., Spessotto, P., Cocchietto, M., Sava, G. Inhibition of B16 melanoma metastases with the ruthenium complex imidazolium trans-imidazoledimethylsulfoxide-tetrachlororuthenate and down-regulation of tumor cell invasion. J. Pharmacol. Exp. Ther. 317, 284-291 (2006).
66. Spessotto, P. et al. EMILIN1 represents a major stromal element determining human trophoblast invasion of the uterine wall. J. Cell Sci. 119, 4574-4584 (2006).