Complement in Metastasis: A Comp in the Camp

Ajona, Daniel; Ortiz‐Espinosa, Sergio; Pı́o, Rubén; Lecanda, Fernando

doi:10.3389/fimmu.2019.00669

Cited by 25 publications

(19 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cancer cells-derived C3a also adapts the cerebrospinal fluid for leptomeningeal metastasis by activation of C3aR on the choroid plexus epithelium, disrupting thus the blood-cerebrospinal fluid barrier 57 . The role of complement for cancer metastases is reviewed elsewhere 58 .…”

Section: Direct Impact Of Complement Effectors On Tumor Cell Biologymentioning

confidence: 99%

Context-dependent roles of complement in cancer

et al. 2019

View full text Add to dashboard Cite

The tumor microenvironment (TME) highly influences the growth, spreading of tumors and therefore patient's clinical outcome. In this context, complement system plays a major and complex role. It may either kill antibody-coated tumor cells or support local inflammation, hamper anti-tumor T cell responses favoring cancer spreading. Recent studies demonstrate that these opposite effects depend of the sites of its activation, the composition of the TME and the tumor cell sensitivity to complement attack. In this review, we present the implication of complement activation and its effects on cancer control and clinical outcome in different TME contexts. We also provide an overview of the publicly available transcriptomic data on the prognostic value of complement genes expression in 30 cancer types. We argue that the interplay of complement within each cancer is unique, governed by the properties of the tumor cells and the TME. This concept is of critical importance for the design of efficient therapeutic strategies.

show abstract

Section: Direct Impact Of Complement Effectors On Tumor Cell Biologymentioning

confidence: 99%

Context-dependent roles of complement in cancer

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Despite this, in recent years advances have been made in understanding the relationship between complement and cancer with several studies demonstrating pro-tumorigenic roles for complement. Several excellent reviews have recently discussed the role of complement in tumour growth and dissemination in detail [3,19,113].…”

Section: Complement In Tumour Growthmentioning

confidence: 99%

“…Furthermore, complement has also been reported to induce angiogenesis [15,119,123] and foster acquisition of an epithelial-mesenchymal transition (EMT) phenotype by promoting expression of stemness genes [122], enhancing invasion [124][125][126] and increasing motility [127][128][129][130] of cells in several cancer types. Detailed overviews of the roles played by complement components in facilitating metastasis have recently been published by Ajona et al [113] and Kochanek et al [131].…”

Section: Murine Studiesmentioning

confidence: 99%

Complement in Tumourigenesis and the Response to Cancer Therapy

O’Brien

Cannon

Reynolds

et al. 2021

Cancers

View full text Add to dashboard Cite

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.

show abstract

“…We also observed a change in the expression of ECM-associated factors in Rreb1 -/embryos, some of which have been linked to changes in the metastatic potential of cells. Furthermore, KEGG pathway analysis of downregulated genes revealed that these were associated with the complement and coagulation cascades, which control a variety of processes, including ECM remodeling, and the corruption of this pathway is linked to cancer metastasis (Ajona, Ortiz-Espinosa, Pio, & Lecanda, 2019). Thus, changes in ECM composition in Rreb1 -/embryos may drive invasive behaviors.…”

Section: Discussionmentioning

confidence: 99%

The transcription factor Rreb1 regulates epithelial architecture, invasiveness, and vasculogenesis in early mouse embryos

Morgani

Nichols

et al. 2021

eLife

View full text Add to dashboard Cite

Ras-responsive element-binding protein 1 (Rreb1) is a zinc-finger transcription factor acting downstream of RAS signaling. Rreb1 has been implicated in cancer and Noonan-like RASopathies. However, little is known about its role in mammalian non-disease states. Here, we show that Rreb1 is essential for mouse embryonic development. Loss of Rreb1 led to a reduction in the expression of vasculogenic factors, cardiovascular defects, and embryonic lethality. During gastrulation, the absence of Rreb1 also resulted in the upregulation of cytoskeleton-associated genes, a change in the organization of F-ACTIN and adherens junctions within the pluripotent epiblast, and perturbed epithelial architecture. Moreover, Rreb1 mutant cells ectopically exited the epiblast epithelium through the underlying basement membrane, paralleling cell behaviors observed during metastasis. Thus, disentangling the function of Rreb1 in development should shed light on its role in cancer and other diseases involving loss of epithelial integrity.

show abstract

Complement in Metastasis: A Comp in the Camp

Cited by 25 publications

References 109 publications

Context-dependent roles of complement in cancer

Context-dependent roles of complement in cancer

Complement in Tumourigenesis and the Response to Cancer Therapy

The transcription factor Rreb1 regulates epithelial architecture, invasiveness, and vasculogenesis in early mouse embryos

Contact Info

Product

Resources

About