C1q–HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 Expression

Vidergar, Romana; Balduit, Andrea; Zacchi, Paola; Agostinis, Chiara; Mangogna, Alessandro; Belmonte, Beatrice; Grandolfo, Micaela; Salton, Francesco; Biolo, Marco; Zanconati, Fabrizio; Confalonieri, Marco; Bulla, Roberta

doi:10.3390/cancers13030416

Cited by 8 publications

(8 citation statements)

References 45 publications

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“…Kou et al [23] through GEO database and the research on Idiopathic Pulmonary Fibrosis (IPF) and non-small cell lung cancer, they found that the prognosis of non-small cell lung cancer and IPF patients with high levels of C1Q is poor. Vidergar et al [24] reported that C1Q promoted the growth of malignant pleural mesothelioma. Besides, in liver cancer, C1Q promoted migratory and invasive phenotypes [25] .…”

Section: Resultsmentioning

confidence: 99%

Impact of Complement C1qA and Complement C1qB on the Prognosis of Osteosarcoma

Wu¹,

Qiu²,

Zeng³

et al. 2023

IJPS

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Impact of Complement C1qA and Complement C1qB on OsteosarcomaIn order to obtain the target gene that affects the prognosis of osteosarcoma and to establish the risk ratio and prognosis of prediction model was the objective of the study. We obtained messenger ribonucleic acid transcriptome data from gene expression Omnibus database and clinical data from therapeutically applicable research to generate effective treatments database. Through intersection of differential genes, we obtained key genes in gene expression Omnibus database and then we used them to conduct survival analysis and establish risk ratio in therapeutically applicable research to generate effective treatments database. We obtained complement C1qA and complement C1qB as the differential key genes through GSE14359, GSE28424, GSE33382 and GSE36001 from gene expression Omnibus database. The expression of complement C1qA and complement C1qB were significantly different in 4 series data (p<0.01). Meanwhile, complement C1qA and complement C1qB have significant correlation in osteosarcoma clinical samples (p=8.61e-64, ρ Spearman =0.97, 95 % confidence interval (0.96-0.98). The survival time of overexpression of complement C1qA and complement C1qB samples were significantly prolonged (p=0.0026 and p=0.006), area under the curve=0.689 (95 % confidence interval, 0.575-0.804), 0.702 (95 % confidence interval, 0.595-0.809), 0.641 (95 % confidence interval, 0.513-0.768) respectively. Complement C1qA and complement C1qB over-expression can significantly prolong survival time and can be used as predictors of survival in osteosarcoma.

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Section: Resultsmentioning

confidence: 99%

Impact of Complement C1qA and Complement C1qB on the Prognosis of Osteosarcoma

Wu¹,

Qiu²,

Zeng³

et al. 2023

IJPS

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“…In gastric cancer cells, hyaluronan synthesis is also associated not only with local and nodal spread but also with reduced survival rates [44]. A marked increase of hyaluronan is also evident in malignant mesothelioma, where it promotes pro-tumourigenic activities [45,46]. Recently, it was also shown that hyaluronan remodels the microenvironment of mesenchymal colorectal tumours, promoting the appearance of a more heterogeneous epithelial environment that favours invasion through interaction with activated fibroblasts [47].…”

Section: Hyaluronan Metabolism Deregulation In Tumoursmentioning

confidence: 99%

Targeting Hyaluronan Synthesis in Cancer: A Road Less Travelled

Karalis

2023

Biologics

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Hyaluronan is one of the major components of the extracellular matrix and is involved in the regulation of multiple processes in both human physiology and disease. In human cancers, hyaluronan metabolism displays remarkable alterations, leading to the accumulation of large amounts of hyaluronan matrices in the tumoural tissues. The altered levels of hyaluronan in the tumours stem from the enhanced expression and activity of hyaluronan synthases in both tumour and stromal cells. Moreover, hyaluronidase activity is also upregulated in cancer, leading to the generation of lower molecular weight hyaluronan fragments that in turn assist tumour growth, neo-angiogenesis and the metastatic cascade. Hyaluronan accumulation in malignant tissues not only assists tumour growth and metastases but is also associated with worse outcomes in cancer patients. Therefore, targeting hyaluronan synthesis emerges as an interesting strategy that might be employed for cancer treatment. This review article summarises current evidence and discusses ways to move forward in the field of targeting hyaluronan synthesis for cancer therapy.

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“…Since HA-bound C1q is capable of modulating HAS expression (27), we aimed at determining whether C1q would impact also on HYAL expression, focusing on the main degradation enzymes, HYAL1 and HYAL2. Moreover, we investigated the involvement of gC1qR as a potential receptor involved in the process.…”

Section: Introductionmentioning

confidence: 99%

Complement protein C1q stimulates hyaluronic acid degradation via gC1qR/HABP1/p32 in malignant pleural mesothelioma

et al. 2023

Self Cite

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Complement component C1q can act as a pro-tumorigenic factor in the tumor microenvironment (TME). The TME in malignant pleural mesothelioma (MPM) is rich in C1q and hyaluronic acid (HA), whose interaction enhances adhesion, migration and proliferation of malignant cells. HA-bound C1q is also capable of modulating HA synthesis. Thus, we investigated whether HA-C1q interaction would affect HA degradation, analyzing the main degradation enzymes, hyaluronidase (HYAL)1 and HYAL2, and a C1q receptor candidate. We first proceeded with the characterization of HYALs in MPM cells, especially HYAL2, since bioinformatics survival analysis revealed that higher HYAL2 mRNA levels have an unfavorable prognostic index in MPM patients. Interestingly, Real-Time quantitative PCR, flow cytometry and Western blot highlighted an upregulation of HYAL2 after seeding of primary MPM cells onto HA-bound C1q. In an attempt to unveil the receptors potentially involved in HA-C1q signaling, a striking co-localization between HYAL2 and globular C1q receptor/HABP1/p32 (gC1qR) was found by immunofluorescence, surface biotinylation and proximity ligation assays. RNA interference experiments revealed a potentially regulatory function exerted by gC1qR on HYAL2 expression, since C1QBP (gene for gC1qR) silencing unexpectedly caused HYAL2 downregulation. In addition, the functional blockage of gC1qR by a specific antibody hindered HA-C1q signaling and prevented HYAL2 upregulation. Thus, C1q-HA interplay is responsible for enhanced HYAL2 expression, suggesting an increased rate of HA catabolism and the release of pro-inflammatory and pro-tumorigenic HA fragments in the MPM TME. Our data support the notion of an overall tumor-promoting property of C1q. Moreover, the overlapping localization and physical interaction between HYAL2 and gC1qR suggests a potential regulatory effect of gC1qR within a putative HA-C1q macromolecular complex.

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C1q–HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 Expression

Cited by 8 publications

References 45 publications

Impact of Complement C1qA and Complement C1qB on the Prognosis of Osteosarcoma

Impact of Complement C1qA and Complement C1qB on the Prognosis of Osteosarcoma

Targeting Hyaluronan Synthesis in Cancer: A Road Less Travelled

Complement protein C1q stimulates hyaluronic acid degradation via gC1qR/HABP1/p32 in malignant pleural mesothelioma

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