Is the Complement Protein C1q a Pro- or Anti-tumorigenic Factor? Bioinformatics Analysis Involving Human Carcinomas

Mangogna, Alessandro; Agostinis, Chiara; Bonazza, Deborah; Belmonte, Beatrice; Zacchi, Paola; Zito, Gabriella; Romano, Andrea; Zanconati, Fabrizio; Ricci, Giuseppe; Kishore, Uday; Bulla, Roberta

doi:10.3389/fimmu.2019.00865

Cited by 55 publications

(44 citation statements)

References 36 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…C1QA and C1QB encode complement C1q subunit A and B, which are the initiator of the classical complement pathway and can induce dendritic cell maturation to generate Th1 type response [56,57]. C1q appears to have pro-tumorigenic and anti-tumorigenic role in cancer, depending on the context of the disease [58]. The anti-cancer role of C1q has been reported in prostate cancer [59], as well as in syngeneic murine model of melanoma [60].…”

Section: Discussionmentioning

confidence: 99%

Expressions of HLA Class II Genes in Cutaneous Melanoma Were Associated with Clinical Outcome: Bioinformatics Approaches and Systematic Analysis of Public Microarray and RNA-Seq Datasets

et al. 2019

View full text Add to dashboard Cite

Major histocompatibility complex (MHC) class II molecules, encoded by human leukocyte antigen (HLA) class II genes, play important roles in antigen presentation and initiation of immune responses. However, the correlation between HLA class II gene expression level and patient survival and disease progression in cutaneous melanoma is still under investigation. In the present study, we analyzed microarray and RNA-Seq data of cutaneous melanoma from The Cancer Genome Atlas (TCGA) using different bioinformatics tools. Survival analysis revealed higher expression level of HLA class II genes in cutaneous melanoma, especially HLA-DP and -DR, was significantly associated with better overall survival. Furthermore, the expressions of HLA class II genes were most closely associated with survival in cutaneous melanoma as compared with other cancer types. The expression of HLA class II co-expressed genes, which were found to associate with antigen processing, immune response, and inflammatory response, was also positively associated with overall survival in cutaneous melanoma. Therefore, the results indicated that increased HLA class II expression may contribute to enhanced anti-tumor immunity and related inflammatory response via presenting tumor antigens to the immune system. The expression pattern of HLA class II genes may serve as a prognostic biomarker and therapeutic targets in cutaneous melanoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Expressions of HLA Class II Genes in Cutaneous Melanoma Were Associated with Clinical Outcome: Bioinformatics Approaches and Systematic Analysis of Public Microarray and RNA-Seq Datasets

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Moreover, lack of C1q in humans, which causes SLE, contributes to uncontrolled CD8 + T cell memory responses, which are not causative in the initial phase of SLE in these patients but rather propagate autoimmune pathology in later stages . C1q has lately garnered high interest beyond those in the complement field because of its involvement in the pathogenesis of several cancers, with both tumor‐promoting or tumor‐protective activities . Thus, there is currently a strong effort to understand how exactly C1q enters cells and what exact molecular mechanisms mediate C1q's effects on mitochondrial activity.…”

Section: The Complosome In Human T Cell Metabolismmentioning

confidence: 99%

Complement and human T cell metabolism: Location, location, location

West

Kunz

Kemper

2020

Immunological Reviews

View full text Add to dashboard Cite

Immunological Reviews. 2020;295:68-81. wileyonlinelibrary.com/journal/imr 1 | INTRODUC TI ON Our contemporary immune system has evolved under the constant pressure from a broad range of pathogens that manipulate the host to enhance their own propagation. As diverse as the pathogenic threats are, ranging from intra-and extracellular bacteria, viruses, fungi, and complex parasites, as elegant and effective are the defense mechanisms developed and employed by the host to combat this constant onslaught. Particularly, the detection systems that are functioning as the first lines of defense against such invaders are formidable. If a microbe has managed to penetrate the protective physical barriers, such as the skin, or lung, a range of innate immune sensors either circulating in the blood, lymph, and interstitial fluids or expressed in and on scavenger and sentinel cells, such as neutrophils and microphages, detect the conserved pathogen-associated molecular patterns (PAMPs). These sensor systems comprise several pattern recognition receptors (PRRs) and include the Toll-like receptors (TLRs), the NOD-like receptors (NLRs), the retinoic acid-inducible gene-I (RIG)-like system, several distinct inflammasomes, and the complement system-derived receptors. 1,2 Activation of PRRs by a pathogen is most often triggered in several sensor systems in parallel and then initiates the general inflammatory reaction as well as tailored immune cell activation specifically effective toward the identified pathogen. The ability of PRR systems to decisively discriminate between a real threat, that is non-self and dangerous self via recognizing so-called danger-associated molecular patterns (DAMPs), and self and harmless alterations of self is critical for our health. Thus, there are several checks and balances build into the PRR systems that prevent unwanted reactions against sensed AbstractThe complement system represents one of the evolutionary oldest arms of our immune system and is commonly recognized as a liver-derived and serum-active system critical for providing protection against invading pathogens. Recent unexpected findings, however, have defined novel and rather "uncommon" locations and activities of complement. Specifically, the discovery of an intracellularly active complement system-the complosome-and its key role in the regulation of cell metabolic pathways that underly normal human T cell responses have taught us that there is still much to be discovered about this system. Here, we summarize the current knowledge about the emerging functions of the complosome in T cell metabolism. We further place complosome activities among the non-canonical roles of other intracellular innate danger sensing systems and argue that a "location-centric" view of complement evolution could logically justify its close connection with the regulation of basic cell physiology. K E Y W O R D S CD46, complement, complosome, metabolism, T cells | 69 WEST ET al.innocuous antigens. However, PRRs not only take care to contain tissue injury during their...

show abstract

“…They highlighted that high levels of C1q had a favorable prognostic role in basal-like breast cancer for disease-free survival as well as in the OS of HER2-positive breast cancer for OS. However, in lung adenocarcinoma and clear cell renal cell carcinoma, C1q performed a pro-tumorigenic role (26). However, little is known on whether C1q plays a direct or indirect role in regulating MM growth.…”

Section: Discussionmentioning

confidence: 99%

Globular C1q Receptor (gC1qR/p32/HABP1) Suppresses the Tumor-Inhibiting Role of C1q and Promotes Tumor Proliferation in 1q21-Amplified Multiple Myeloma

Sun

Jiang

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

Immunodeficiencies are widely becoming known as important features of multiple myeloma (MM) and may promote the proliferation of malignant cells as well as confer resistance to therapy. Few studies focus on the immunomodulatory effects of the complement system on MM. This study aims to explore the role of C1q in MM patients. Plasma C1q was found to be significantly reduced in MM patients, and the amount of C1q deposited around the CD138 + cells in bone marrow (BM) biopsy sections was observed to be much higher, especially in the subgroup with 1q21 amplification (Amp1q21). CD138 + cells expressed higher levels of C1q receptors (C1qRs) than CD138 − cells. Patients with Amp1q21 expressed higher levels of globular C1qR (gC1qR), whereas patients without Amp21 expressed higher levels of collagen tail C1qR (cC1qR). Additionally, gC1qR was noted to suppress the MM-inhibiting role of C1q in H929, U266, and MM1S. gC1qR interacts with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), which also suppressed the function of C1q and regulated CDC28 protein kinase regulatory subunit 1B (CKS1B) mRNA. In summary, gC1qR suppressed the MM-inhibiting role of C1q and regulated CKS1B mRNA in promoting tumor proliferation via IGF2BP3 in 1q21-amplified MM. Our findings provide novel evidence on how MM cells evade the immune system and promote survival as well as suggest possible novel targets for future therapies of MM.

show abstract

Is the Complement Protein C1q a Pro- or Anti-tumorigenic Factor? Bioinformatics Analysis Involving Human Carcinomas

Cited by 55 publications

References 36 publications

Expressions of HLA Class II Genes in Cutaneous Melanoma Were Associated with Clinical Outcome: Bioinformatics Approaches and Systematic Analysis of Public Microarray and RNA-Seq Datasets

Expressions of HLA Class II Genes in Cutaneous Melanoma Were Associated with Clinical Outcome: Bioinformatics Approaches and Systematic Analysis of Public Microarray and RNA-Seq Datasets

Complement and human T cell metabolism: Location, location, location

Globular C1q Receptor (gC1qR/p32/HABP1) Suppresses the Tumor-Inhibiting Role of C1q and Promotes Tumor Proliferation in 1q21-Amplified Multiple Myeloma

Contact Info

Product

Resources

About