Activation of the complement system in an osteosarcoma cell line promotes angiogenesis through enhanced production of growth factors

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

There is increasing evidence that the complement system is activated in various cancer tissues. Besides being involved in innate immunity against pathogens, the complement system also participates in inflammation and the modulation of tumor microenvironment. Recent studies suggest that complement activation promotes tumor progression in various ways. Among some cancer cell lines, we found that human bone osteosarcoma epithelial cells (U2-OS) can activate the alternative pathway of the complement system by pooled normal human serum. Interestingly, U2-OS cells showed less expression of complement regulatory proteins, compared to other cancer cell lines. Furthermore, the activated complement system enhanced the production of growth factors, which promoted angiogenesis of human endothelial cells. Our results demonstrated a direct linkage between the complement system and angiogenesis using the in vitro model, which suggest the complement system and related mechanisms might be potential targets for cancer treatment.

Related collections

Most cited references 25

Record: found
Abstract: found
Article: found

Is Open Access

Complement System Part II: Role in Immunity

Nicolas S. Merle, Remi Noe, Lise Halbwachs-Mecarelli … (2015)

The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b–9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target.

0 comments Cited 389 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Cancer and the complement cascade.

Martin Rutkowski, Michael E. Sughrue, Ari J. Kane … (2010)

Despite significant research on the role of inflammation and immunosurveillance in the immunologic microenvironment of tumors, little attention has been given to the oncogenic capabilities of the complement cascade. The recent finding that complement may contribute to tumor growth suggests an insidious relationship between complement and cancer, especially in light of evidence that complement facilitates cellular proliferation and regeneration. We address the hypothesis that complement proteins promote carcinogenesis and suggest mechanisms by which complement can drive the fundamental features of cancer. Evidence shows that this diverse family of innate immune proteins facilitates dysregulation of mitogenic signaling pathways, sustained cellular proliferation, angiogenesis, insensitivity to apoptosis, invasion and migration, and escape from immunosurveillance. Given that the traditionally held functions for the complement system include innate immunity and cancer defense, our review suggests a new way of thinking about the role of complement proteins in neoplasia. ©2010 AACR.

0 comments Cited 88 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly.

Dirk Spitzer, John P. Atkinson, Nadia L. Mitchell … (2007)

Complement promotes the rapid recognition and elimination of pathogens, infected cells, and immune complexes. The biochemical basis for its target specificity is incompletely understood. In this report, we demonstrate that properdin can directly bind to microbial targets and provide a platform for the in situ assembly and function of the alternative pathway C3 convertases. This mechanism differs from the standard model wherein nascent C3b generated in the fluid phase attaches nonspecifically to its targets. Properdin-directed complement activation occurred on yeast cell walls (zymosan) and Neisseria gonorrhoeae. Properdin did not bind wild-type Escherichia coli, but it readily bound E. coli LPS mutants, and the properdin-binding capacity of each strain correlated with its respective serum-dependent AP activation rate. Moreover, properdin:single-chain Ab constructs were used to direct serum-dependent complement activation to novel targets. We conclude properdin participates in two distinct complement activation pathways: one that occurs by the standard model and one that proceeds by the properdin-directed model. The properdin-directed model is consistent with a proposal made by Pillemer and his colleagues >50 years ago.

0 comments Cited 70 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Myung-Shin Lee:

ORCID: http://orcid.org/0000-0001-9145-6190

mslee@eulji.ac.kr

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 3 April 2018

Publication date PMC-release: 3 April 2018

Publication date Collection: 2018

Volume: 8

Electronic Location Identifier: 5415

Affiliations

[1 ]ISNI 0000 0004 1798 4296, GRID grid.255588.7, Department of Microbiology and Immunology, , Eulji University School of Medicine, ; Daejeon, 34824 South Korea

[2 ]ISNI 0000 0004 1798 4296, GRID grid.255588.7, Eulji Biomedical Science Research Institute, , Eulji University School of Medicine, ; Daejeon, 34824 Republic of Korea

[3 ]ISNI 0000 0004 1798 4296, GRID grid.255588.7, Department of Pathology, , Eulji University School of Medicine, ; Daejeon, 34824 South Korea

Author information

Myung-Shin Lee http://orcid.org/0000-0001-9145-6190

Article

Publisher ID: 23851

DOI: 10.1038/s41598-018-23851-z

PMC ID: 5883033

PubMed ID: 29615744

SO-VID: d75b2fa4-54d8-4ccd-a6fd-9415056e1e1d

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 5 January 2018

Date accepted : 21 March 2018

Custom metadata

ScienceOpen disciplines: Uncategorized

Data availability:

ScienceOpen disciplines: Uncategorized

Comments

Comment on this article

scite_

Cited by 17

See all cited by

Activation of the complement system in an osteosarcoma cell line promotes angiogenesis through enhanced production of growth factors

Read this article at

Abstract

Related collections

Sunway University Press

Most cited references 25

Complement System Part II: Role in Immunity

Cancer and the complement cascade.

Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 385

Cited by 17