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Article: Type III TGF-β receptor down-regulation promoted tumor progression via complement component C5a induction in hepatocellular carcinoma
Title | Type III TGF-β receptor down-regulation promoted tumor progression via complement component C5a induction in hepatocellular carcinoma |
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Authors | |
Keywords | Clinical outcomes Tumor-suppressive protein Diagnosis prediction Therapeutic potential Complement component |
Issue Date | 2021 |
Publisher | MDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/ |
Citation | Cancers, 2021, v. 13 n. 7, article no. 1503 How to Cite? |
Abstract | Background and Aims—Transforming growth factor-beta (TGF-β) signaling orchestrates tumorigenesis and one of the family members, TGF-β receptor type III (TGFβR3), are distinctively under-expressed in numerous malignancies. Currently, the clinical impact of TGFβR3 down-regulation and the underlying mechanism remains unclear in hepatocellular carcinoma (HCC). Here, we aimed to identify the tumor-promoting roles of decreased TGFβR3 expression in HCC progression. Materials and Methods—For clinical analysis, plasma and liver specimens were collected from 100 HCC patients who underwent curative resection for the quantification of TGFβR3 by q-PCR and ELISA. To study the tumor-promoting mechanism of TGFβR3 downregulation, HCC mouse models and TGFβR3 knockout cell lines were applied. Results—Significant downregulation of TGFβR3 and its soluble form (sTGFβR3) were found in HCC tissues and plasma compared to healthy individuals (p < 0.01). Patients with <9.4 ng/mL sTGFβR3 exhibited advanced tumor stage, higher recurrence rate and shorter disease-free survival (p < 0.05). The tumor-suppressive function of sTGFβR3 was further revealed in an orthotopic mouse HCC model, resulting in 2-fold tumor volume reduction. In TGFβR3 knockout hepatocyte and HCC cells, increased complement component C5a was observed and strongly correlated with shorter survival and advanced tumor stage (p < 0.01). Interestingly, C5a activated the tumor-promoting Th-17 response in tumor associated macrophages. Conclusion—TGFβR3 suppressed tumor progression, and decreased expression resulted in poor prognosis in HCC patients through upregulation of tumor-promoting complement C5a. |
Persistent Identifier | http://hdl.handle.net/10722/304756 |
ISSN | 2023 Impact Factor: 4.5 2023 SCImago Journal Rankings: 1.391 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Yeung, OWH | - |
dc.contributor.author | Qi, X | - |
dc.contributor.author | Pang, L | - |
dc.contributor.author | Liu, H | - |
dc.contributor.author | Ng, KTP | - |
dc.contributor.author | Liu, J | - |
dc.contributor.author | Lo, CM | - |
dc.contributor.author | Man, K | - |
dc.date.accessioned | 2021-10-05T02:34:44Z | - |
dc.date.available | 2021-10-05T02:34:44Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Cancers, 2021, v. 13 n. 7, article no. 1503 | - |
dc.identifier.issn | 2072-6694 | - |
dc.identifier.uri | http://hdl.handle.net/10722/304756 | - |
dc.description.abstract | Background and Aims—Transforming growth factor-beta (TGF-β) signaling orchestrates tumorigenesis and one of the family members, TGF-β receptor type III (TGFβR3), are distinctively under-expressed in numerous malignancies. Currently, the clinical impact of TGFβR3 down-regulation and the underlying mechanism remains unclear in hepatocellular carcinoma (HCC). Here, we aimed to identify the tumor-promoting roles of decreased TGFβR3 expression in HCC progression. Materials and Methods—For clinical analysis, plasma and liver specimens were collected from 100 HCC patients who underwent curative resection for the quantification of TGFβR3 by q-PCR and ELISA. To study the tumor-promoting mechanism of TGFβR3 downregulation, HCC mouse models and TGFβR3 knockout cell lines were applied. Results—Significant downregulation of TGFβR3 and its soluble form (sTGFβR3) were found in HCC tissues and plasma compared to healthy individuals (p < 0.01). Patients with <9.4 ng/mL sTGFβR3 exhibited advanced tumor stage, higher recurrence rate and shorter disease-free survival (p < 0.05). The tumor-suppressive function of sTGFβR3 was further revealed in an orthotopic mouse HCC model, resulting in 2-fold tumor volume reduction. In TGFβR3 knockout hepatocyte and HCC cells, increased complement component C5a was observed and strongly correlated with shorter survival and advanced tumor stage (p < 0.01). Interestingly, C5a activated the tumor-promoting Th-17 response in tumor associated macrophages. Conclusion—TGFβR3 suppressed tumor progression, and decreased expression resulted in poor prognosis in HCC patients through upregulation of tumor-promoting complement C5a. | - |
dc.language | eng | - |
dc.publisher | MDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/ | - |
dc.relation.ispartof | Cancers | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Clinical outcomes | - |
dc.subject | Tumor-suppressive protein | - |
dc.subject | Diagnosis prediction | - |
dc.subject | Therapeutic potential | - |
dc.subject | Complement component | - |
dc.title | Type III TGF-β receptor down-regulation promoted tumor progression via complement component C5a induction in hepatocellular carcinoma | - |
dc.type | Article | - |
dc.identifier.email | Yeung, OWH: why21@hku.hk | - |
dc.identifier.email | Liu, H: liuhui25@hku.hk | - |
dc.identifier.email | Ng, KTP: ledodes@hku.hk | - |
dc.identifier.email | Liu, J: liujiang@hku.hk | - |
dc.identifier.email | Lo, CM: chungmlo@hkucc.hku.hk | - |
dc.identifier.email | Man, K: kwanman@hku.hk | - |
dc.identifier.authority | Ng, KTP=rp01720 | - |
dc.identifier.authority | Lo, CM=rp00412 | - |
dc.identifier.authority | Man, K=rp00417 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.3390/cancers13071503 | - |
dc.identifier.pmid | 33805946 | - |
dc.identifier.pmcid | PMC8037431 | - |
dc.identifier.scopus | eid_2-s2.0-85103028171 | - |
dc.identifier.hkuros | 325959 | - |
dc.identifier.volume | 13 | - |
dc.identifier.issue | 7 | - |
dc.identifier.spage | article no. 1503 | - |
dc.identifier.epage | article no. 1503 | - |
dc.identifier.isi | WOS:000638371200001 | - |
dc.publisher.place | Switzerland | - |