scholarly journals Complement System: Promoter or Suppressor of Cancer Progression?

Antibodies ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 57
Author(s):  
Margot Revel ◽  
Marie V. Daugan ◽  
Catherine Sautés-Fridman ◽  
Wolf H. Fridman ◽  
Lubka T. Roumenina
Keyword(s):  
Cancer Progression ◽  
Complement System ◽  
Current Knowledge ◽  
Prognostic Impact ◽  
Cancer Type ◽  
Human Cancers ◽  
Cancer Types ◽  
The Complement System

Constituent of innate immunity, complement is present in the tumor microenvironment. The functions of complement include clearance of pathogens and maintenance of homeostasis, and as such could contribute to an anti-tumoral role in the context of certain cancers. However, multiple lines of evidence show that in many cancers, complement has pro-tumoral actions. The large number of complement molecules (over 30), the diversity of their functions (related or not to the complement cascade), and the variety of cancer types make the complement-cancer topic a very complex matter that has just started to be unraveled. With this review we highlight the context-dependent role of complement in cancer. Recent studies revealed that depending of the cancer type, complement can be pro or anti-tumoral and, even for the same type of cancer, different models presented opposite effects. We aim to clarify the current knowledge of the role of complement in human cancers and the insights from mouse models. Using our classification of human cancers based on the prognostic impact of the overexpression of complement genes, we emphasize the strong potential for therapeutic targeting the complement system in selected subgroups of cancer patients.

scholarly journals Complement System in Cutaneous Squamous Cell Carcinoma

2019 ◽  
Vol 20 (14) ◽  
pp. 3550 ◽  
Author(s):  
Pilvi Riihilä ◽  
Liisa Nissinen ◽  
Jaakko Knuutila ◽  
Pegah Rahmati Nezhad ◽  
Kristina Viiklepp ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Immune Responses ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Complement System ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Complement Components ◽  
The Complement System

Epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer with high mortality rates in the advanced stage. Chronic inflammation is a recognized risk factor for cSCC progression and the complement system, as a part of innate immunity, belongs to the microenvironment of tumors. The complement system is a double-edged sword in cancer, since complement activation is involved in anti-tumor cytotoxicity and immune responses, but it also promotes cancer progression directly and indirectly. Recently, the role of several complement components and inhibitors in the regulation of progression of cSCC has been shown. In this review, we will discuss the role of complement system components and inhibitors as biomarkers and potential new targets for therapeutic intervention in cSCC.

scholarly journals Complement in Tumourigenesis and the Response to Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1209
Author(s):  
Rebecca M. O’Brien ◽  
Aoife Cannon ◽  
John V. Reynolds ◽  
Joanne Lysaght ◽  
Niamh Lynam-Lennon
Keyword(s):  
Immune Cells ◽  
Complement System ◽  
Immune Cell ◽  
Tumour Microenvironment ◽  
Cancer Type ◽  
Combination Therapies ◽  
Metastatic Phenotype ◽  
Complement Components ◽  
The Complement System

In recent years, our knowledge of the complement system beyond innate immunity has progressed significantly. A modern understanding is that the complement system has a multifaceted role in malignancy, impacting carcinogenesis, the acquisition of a metastatic phenotype and response to therapies. The ability of local immune cells to produce and respond to complement components has provided valuable insights into their regulation, and the subsequent remodeling of the tumour microenvironment. These novel discoveries have advanced our understanding of the immunosuppressive mechanisms supporting tumour growth and uncovered potential therapeutic targets. This review discusses the current understanding of complement in cancer, outlining both direct and immune cell-mediated roles. The role of complement in response to therapies such as chemotherapy, radiation and immunotherapy is also presented. While complement activities are largely context and cancer type-dependent, it is evident that promising therapeutic avenues have been identified, in particular in combination therapies.

scholarly journals Role of the Complement System in the Response to Orthopedic Biomaterials

2018 ◽  
Vol 19 (11) ◽  
pp. 3367 ◽  
Author(s):  
Yvonne Mödinger ◽  
Graciosa Teixeira ◽  
Cornelia Neidlinger-Wilke ◽  
Anita Ignatius
Keyword(s):  
Complement System ◽  
Bone Cells ◽  
Current Knowledge ◽  
Target Cells ◽  
Host Immune System ◽  
Bone Homeostasis ◽  
Orthopedic Medicine ◽  
Almost All ◽  
The Complement System

Various synthetic biomaterials are used to replace lost or damaged bone tissue that, more or less successfully, osseointegrate into the bone environment. Almost all biomaterials used in orthopedic medicine activate the host-immune system to a certain degree. The complement system, which is a crucial arm of innate immunity, is rapidly activated by an implanted foreign material into the human body, and it is intensely studied regarding blood-contacting medical devices. In contrast, much less is known regarding the role of the complement system in response to implanted bone biomaterials. However, given the increasing knowledge of the complement regulation of bone homeostasis, regeneration, and inflammation, complement involvement in the immune response following biomaterial implantation into bone appears very likely. Moreover, bone cells can produce complement factors and are target cells of activated complement. Therefore, new bone formation or bone resorption around the implant area might be greatly influenced by the complement system. This review aims to summarize the current knowledge on biomaterial-mediated complement activation, with a focus on materials primarily used in orthopedic medicine. In addition, methods to modify the interactions between the complement system and bone biomaterials are discussed, which might favor osseointegration and improve the functionality of the device.

scholarly journals Regulation of Rho GTPases by RhoGDIs in Human Cancers

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1037 ◽  
Author(s):  
Cho ◽  
Kim ◽  
Baek ◽  
Kim ◽  
Lee
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Mechanisms ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Human Cancers

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

scholarly journals miR-205 in Breast Cancer: State of the Art

2020 ◽  
Vol 22 (1) ◽  
pp. 27
Author(s):  
Ilaria Plantamura ◽  
Alessandra Cataldo ◽  
Giulia Cosentino ◽  
Marilena V. Iorio
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Normal Breast ◽  
Response To Therapy ◽  
Aberrant Expression ◽  
Open Questions ◽  
Tumor Tissues ◽  
Breast Physiology ◽  
Cancer Types

Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.

scholarly journals Special Issue: The Role of Complement in Cancer Immunotherapy

Antibodies ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 29
Author(s):  
Ronald P. Taylor
Keyword(s):  
Cancer Immunotherapy ◽  
Complement System ◽  
Immune Defense ◽  
Special Issue ◽  
The Complement System ◽  
Critical Aspects

The complement system plays an important role in critical aspects of immune defense and in the maintenance of homeostasis in the bloodstream, as well as in essentially all tissues and organs [...]

The role of the complement system in hereditary angioedema

2017 ◽  
Vol 89 ◽  
pp. 59-68 ◽  
Author(s):  
Dorottya Csuka ◽  
Nóra Veszeli ◽  
Lilian Varga ◽  
Zoltán Prohászka ◽  
Henriette Farkas
Keyword(s):  
Complement System ◽  
Hereditary Angioedema ◽  
The Complement System

scholarly journals Role of the NUDT Enzymes in Breast Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2267
Author(s):  
Roni H. G. Wright ◽  
Miguel Beato
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Breast Cancers ◽  
Metastatic Colonization ◽  
Hormone Receptor Positive ◽  
Aggressive Cancer ◽  
Cancer Types ◽  
Metastatic Process

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

scholarly journals Activated Rho GTPases in Cancer—The Beginning of a New Paradigm

2018 ◽  
Vol 19 (12) ◽  
pp. 3949 ◽  
Author(s):  
Pontus Aspenström
Keyword(s):  
Cancer Progression ◽  
Rho Gtpases ◽  
Current Knowledge ◽  
Small Gtpases ◽  
Cell Morphogenesis ◽  
New Paradigm ◽  
Direct Involvement ◽  
Cell Locomotion ◽  
Human Cancers ◽  
Cytoskeletal Dynamics

Involvement of Rho GTPases in cancer has been a matter of debate since the identification of the first members of this branch of the Ras superfamily of small GTPases. The Rho GTPases were ascribed important roles in the cell, although these were restricted to regulation of cytoskeletal dynamics, cell morphogenesis, and cell locomotion, with initially no clear indications of direct involvement in cancer progression. This paradigm has been challenged by numerous observations that Rho-regulated pathways are often dysregulated in cancers. More recently, identification of point mutants in the Rho GTPases Rac1, RhoA, and Cdc42 in human tumors has finally given rise to a new paradigm, and we can now state with confidence that Rho GTPases serve as oncogenes in several human cancers. This article provides an exposé of current knowledge of the roles of activated Rho GTPases in cancers.

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