Role of thrombospondin‐1 expression in colorectal liver metastasis and its molecular mechanism

Teraoku, Hiroki; Morine, Yuji; Ikemoto, Tetsuya; Saito, Yu; Yamada, Shinichiro; Yoshikawa, Masaharu; Takasu, Chie; Higashijima, Jun; Imura, Satoru

doi:10.1002/jhbp.376

Cited by 20 publications

(19 citation statements)

References 49 publications

(60 reference statements)

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“…Members of the thrombospondin family previously have been associated with differential expression in different CRC phenotypes; THBS4 has been associated with CIMP high tumors, of which a subset are mismatch repair deficient [ 56 ]. THBS1 has previously been associated with the development of the tumor micro-environment and angiogenesis [ 57 ] and metastasis [ 15 ]. AMH was upregulated in all tumors, but had lower expression levels in MSS tumors and the highest expression levels in MSI tumors.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we show that miRNAs play a role in the TGFβ’s function in CRC development, supporting earlier findings. Most earlier studies have focused on one, or several miRNAs such as miR-21 and miR-155 [ 65 ], miR-590 [ 28 ], miR-17-92 [ 29 ] and miR-494 and miR-126-5p [ 26 ] or else focus on select genes in the TGFβ pathway, such as THBS1 [ 15 ]. Here we assessed the associations between every gene in the KEGG TGFβ-signaling pathway and the expression levels of over 800 miRNAs.…”

Section: Discussionmentioning

confidence: 99%

“…BMPR1A has been reported as being inactivated in some studies focusing on familial syndromes such as mixed polyposis syndrome and familial juvenile polyposis [ 11 – 13 ]. Other factors that regulate TGFβ and its receptors are BAMBI (BMP and activing membrane bound inhibitor) [ 14 ], THBS1 (thrombospondin 1 also known as TSP1) [ 15 ], LEFTY (left–right determination factor, Factor 2 also known as TGFβ4) [ 16 ], and FST (Follistatin) [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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The TGFβ-signaling pathway and colorectal cancer: associations between dysregulated genes and miRNAs

et al. 2018

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BackgroundThe TGFβ-signaling pathway plays an important role in the pathogenesis of colorectal cancer (CRC). Loss of function of several genes within this pathway, such as bone morphogenetic proteins (BMPs) have been seen as key events in CRC progression.MethodsIn this study we comprehensively evaluate differential gene expression (RNASeq) of 81 genes in the TGFβ-signaling pathway and evaluate how dysregulated genes are associated with miRNA expression (Agilent Human miRNA Microarray V19.0). We utilize paired carcinoma and normal tissue from 217 CRC cases. We evaluate the associations between differentially expressed genes and miRNAs and sex, age, disease stage, and survival months.ResultsThirteen genes were significantly downregulated and 14 were significantly upregulated after considering fold change (FC) of > 1.50 or < 0.67 and multiple comparison adjustment. Bone morphogenetic protein genes BMP5, BMP6, and BMP2 and growth differentiation factor GDF7 were downregulated. BMP4, BMP7, INHBA (Inhibin beta A), TGFBR1, TGFB2, TGIF1, TGIF2, and TFDP1 were upregulated. In general, genes with the greatest dysregulation, such as BMP5 (FC 0.17, BMP6 (FC 0.25), BMP2 (FC 0.32), CDKN2B (FC 0.32), MYC (FC 3.70), BMP7 (FC 4.17), and INHBA (FC 9.34) showed dysregulation in the majority of the population (84.3, 77.4, 81.1, 80.2, 82.0, 51.2, and 75.1% respectively). Four genes, TGFBR2, ID4, ID1, and PITX2, were un-associated or slightly upregulated in microsatellite-stable (MSS) tumors while downregulated in microsatellite-unstable (MSI) tumors. Eight dysregulated genes were associated with miRNA differential expression. E2F5 and THBS1 were associated with one or two miRNAs; RBL1, TGFBR1, TGIF2, and INHBA were associated with seven or more miRNAs with multiple seed-region matches. Evaluation of the joint effects of mRNA:miRNA identified interactions that were stronger in more advanced disease stages and varied by survival months.ConclusionThese data support an interaction between miRNAs and genes in the TGFβ-signaling pathway in association with CRC risk. These interactions are associated with unique clinical characteristics that may provide targets for further investigations.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1566-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The TGFβ-signaling pathway and colorectal cancer: associations between dysregulated genes and miRNAs

et al. 2018

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“…THBS1 and PSPN are also highly detected in the PVC-CM. THBS1, a glycoprotein, is implicated in the regulation of tumor growth and metastasis [1523]. PSPN was first identified as a glial cell line-derived neurotrophic factor (GDNF) that had neurotrophic effects on some neuronal cell types.…”

Section: Discussionmentioning

confidence: 99%

Paracrine influence of human perivascular cells on the proliferation of adenocarcinoma alveolar epithelial cells

EunbiKim

SunghunNa

BorimAn

et al. 2017

Korean J Physiol Pharmacol

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Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-1α and K562) in vitro using Transwell® co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-1α and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer.

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“…The data of HR and 95% CI was extracted from survival curves or literature reports. In all these studies, 17 studies researched OS [17,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37], 7 studies investigated DFS/RFS [22,23,26,[38][39][40][41] and 6 studies focused on progression-free survival (PFS)/ metastasis-free survival (MFS) [28,31,32,[42][43][44] (Table 2).…”

Section: Study Characteristicsmentioning

confidence: 99%

Role of TSP-1 as prognostic marker in various cancers: a systematic review and meta-analysis

et al. 2020

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Background: Published studies present conflicting data regarding the impact of Thrombospondin-1 (TSP-1) expression on prognosis of various cancers. We performed this meta-analysis to illustrate the preliminary predictive value of TSP-1. Methods: Twenty-four studies with a total of 2379 patients were included. A comprehensive literature search was performed by using PubMed, Cochrane Library, Web of Science, Embase, and hand searches were also conducted of relevant bibliographies. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for patient survival and disease recurrence were initially identified to explore relationships between TSP-1 expression and patient prognosis. Results: A total of 24 eligible studies were included in this meta-analysis. Our results showed that high level of TSP-1 was correlated significantly with poor overall survival (OS) (HR = 1.40, 95% CI: 1.17~1.68; P<0.001). However, high TSP-1 expression predicted no significant impact on progression-free survival (PFS)/ metastasis-free survival (MFS) (HR = 1.35, 95%CI: 0.87-2.10; P = 0.176) and disease-free survival (DFS)/ recurrence-free survival (RFS) (HR = 1.40, 95%CI: 0.77-2.53; P = 0.271). In addition, we performed subgroup analyses which showed that high TSP-1 expression predicted poor prognosis in breast cancer and gynecological cancer. Additionally, the relatively small number of studies on PFS/MFS and DFS/RFS is a limitation. The data extracted through Kaplan-Meier curves may not be accurate. Moreover, only English articles were included in this article, which may lead to deviations in the results. Conclusions: Our findings indicated high TSP-1 expression may act as a promising biomarker of poor prognosis in cancers, especially in breast cancer and gynecological cancer.

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Role of thrombospondin‐1 expression in colorectal liver metastasis and its molecular mechanism

Abstract: Low THBS-1 expression may be an independent poor prognostic factor that affects tumor growth and EMT acquisition. Additionally, THBS-1 may be regulated by the HIF-1 pathway.

Cited by 20 publications

References 49 publications

The TGFβ-signaling pathway and colorectal cancer: associations between dysregulated genes and miRNAs

The TGFβ-signaling pathway and colorectal cancer: associations between dysregulated genes and miRNAs

Paracrine influence of human perivascular cells on the proliferation of adenocarcinoma alveolar epithelial cells

Role of TSP-1 as prognostic marker in various cancers: a systematic review and meta-analysis

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