Hepatocyte growth factor enhances ovarian cancer cell invasion through down-regulation of thrombospondin-1

Wei, Wei; Kong, Beihua; Yang, Qifeng; Qu, Xun

doi:10.4161/cbt.9.2.10280

Cited by 20 publications

(20 citation statements)

References 61 publications

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“…Additionally, certain peptides derived from TSP-1, such as type I repeats [19] and CSVTCG sequence [13], are known to bind to MMP-9 and inhibit its activation. In regards to the role of TSP-1 in regulating MMP-9 in cancer cells, there were several opinions that TSP-1 acts as an inhibitor in breast cancer [19] and ovarian cancer [20]. In UC, TSP-1 expression was found to be negatively correlated with MMP-9 expression [16].…”

Section: Discussionmentioning

confidence: 99%

“…In fact, increased MMP-9 levels have been reported to be closely associated with high stages of cancer in various human tissues, including UC-UUT [16,18]. However, as with angiogenesis, TSP-1 appears to have dual roles in the regulation of MMP-9 function in cancer, that is, either as a stimulator [13,15] or an inhibitor [19,20]. In regards to TSP-1 and tumour growth, there are several reports suggesting that TSP-1 may inhibit cancer cell proliferation in several cancers [21,22].…”

Section: Introductionmentioning

confidence: 99%

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Thrombospondin-1-derived 4N1K peptide expression is negatively associated with malignant aggressiveness and prognosis in urothelial carcinoma of the upper urinary tract

et al. 2012

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BackgroundThrombospondin (TSP) is a multi-functional protein that appears to have dual roles in cancer, that is, either as a promoter or a suppressor. 4N1K is a TSP-derived peptide that has been reported to be associated with neovascularity, cell survival, and invasion. There is a little information regarding its pathological roles in human cancer tissues. Our aim was to clarify clinical significance and prognostic value of 4N1K expression in patients with urothelial carcinoma of the upper urinary tract (UC-UUT).MethodsWe investigated 4N1K expression in 97 surgically excised, non-metastasized UC-UUT specimens and five normal tissues via immunohistochemistry. Microvessel density (MVD), lymph vessel density (LVD), cancer cell proliferation (PI), apoptotic index (AI), and matrix metalloproteinase (MMP)-9 expression was also determined. The relationships 4N1K expression and pT stage, grade, and prognosis were analysed. In addition, correlations with these cancer-related and TSP-related factors were also investigated.ResultsStrong and moderate 4N1K expression was found in normal urothelial tissues. Of the 97 specimens, 45 patients were positive for 4N1K expression, which was primarily located in the interstitial areas of the cancer tissue. 4N1K expression was negatively associated with pT stage (p = 0.003) and grade (p = 0.002). Survival analyses revealed that 4N1K is a predictor of metastasis-free (p = 0.036) and cause-specific survival (p = 0.009). 4N1K expression was closely associated with malignant behaviour, specifically MVD (p = 0.001), AI (p = 0.013), and MMP-9 expression (p = 0.036), but not PI and LVD, as determined via multivariate analysis models.Conclusions4N1K expression appears to be associated with cancer cell progression and survival in UC-UUT patients via the regulation of angiogenesis, apoptosis, and MMP-9 expression. There is a possibility that the 4N1K-peptide may be a useful marker and novel therapeutic target in patients with UC-UUT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thrombospondin-1-derived 4N1K peptide expression is negatively associated with malignant aggressiveness and prognosis in urothelial carcinoma of the upper urinary tract

et al. 2012

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“…However, multiple receptors engaged by TSP-1 makes this function differ based on cell types such that an inhibitory effect on cellular migration is reported in the case of vascular endothelial cells 31 and dendritic cells 32 , while promotion of migration is noted in the case of neural crest cells 33 , fibroblasts 34 , corneal endothelial cells 35 and T cells 36 . In the case of tumor cells migration is correlated with metastasis; with inhibition reported in some tumor cells 37 and tumor progression in others 38, 39 . These differences are partly due to the fact that tumor cell migration is downstream of other functions influenced by TSP-1 such as activation of latent TGF-β, inhibition of angiogenesis or up-regulation of matrix metalloproteinases 40 .…”

Section: Introductionmentioning

confidence: 98%

Matricellular Protein Thrombospondins: Influence on Ocular Angiogenesis, Wound Healing and Immuneregulation

Masli

Cursiefen

Zieske

2014

Current Eye Research

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Thrombospondins are a family of large multi-domain glycoproteins described as matricelluar proteins based on their ability to interact with a broad range of receptors, matrix molecules, growth factors or proteases and to modulate array of cellular functions including intracellular signaling, proliferation and migration. Two members of the thrombospondin family, thrombospondin 1 (TSP1) and thrombospondin 2 (TSP2) are studied extensively to determine their structure and function. While expressed at low levels in normal adult tissues their increased expression is seen predominantly in response to cellular perturbations. Despite structural similarities a notable functional difference between TSP1 and TSP2 includes the ability of former to activate of latent TGF-β and its competitive inhibition by the latter. Both these thrombospondins are reported to play important roles in TGF-β rich ocular environment with most reports related to TSP1. Expressed by many ocular cell types and detectable in the aqueous and vitreous humor TSP1 and TSP2 influence many cellular interactions in the eye such as angiogenesis, cell migration, wound healing, TGF-β activation and regulation of inflammatory immune responses. Together these processes are known to contribute to the immune privilege status of the eye. Emerging roles of TSP1 and TSP2 in ocular functions and pathology are reviewed here.

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“…Navab et al found that the co-expression of Met and HGF promoted systemic metastasis in NCI-H4650, a human non-small cell lung carcinoma cell line [27]. High levels of HGF have also been found in pancreatic cancer [28] and are related to the invasion of ovarian cancer cell [29] and human mammary ductal carcinoma [30]. The HGF inhibitors are considered to have therapeutic potential in cancers [31].…”

Section: Introductionmentioning

confidence: 99%

Claudin-7 inhibits human lung cancer cell migration and invasion through ERK/MAPK signaling pathway

Lü

Ding

Hong

et al. 2011

Experimental Cell Research

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Tight junctions are the most apical component of the junctional complex critical for epithelial cell barrier and polarity functions. Although its disruption is well documented during cancer progression such as epithelial-mesenchymal transition, molecular mechanisms by which tight junction integral membrane protein claudins affect this process remain largely unknown. In this report, we found that claudin-7 was normally expressed in bronchial epithelial cells of human lungs but was either downregulated or disrupted in its distribution pattern in lung cancer. To investigate the function of claudin-7 in lung cancer cells, we transfected claudin-7 cDNA into NCI-H1299, a human lung carcinoma cell line that has no detectable claudin-7 expression. We found that claudin-7 expressing cells showed a reduced response to hepatocyte growth factor (HGF) treatment, were less motile, and formed fewer foot processes than the control cells did. In addition, cells transfected with claudin-7 dramatically decreased their invasive ability after HGF treatment. These effects were mediated through the MAPK signaling pathway since the phosphorylation level of ERK1/2 was significantly lower in claudin-7 transfected cells than in control cells. PD98059, a selective inhibitor of ERK/MAPK pathway, was able to block the motile effect. Claudin-7 formed stable complexes with claudin-1 and -3 and was able to recruit them to the cell-cell junction area in claudin-7 transfected cells. When control and claudin-7 transfected cells were inoculated into nude mice, claudin-7 expressing cells produced smaller tumors than the control cells. Taken together, our study demonstrates that claudin-7 inhibits cell migration and invasion through ERK/MAPK signaling pathway in response to growth factor stimulation in human lung cancer cells.

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Hepatocyte growth factor enhances ovarian cancer cell invasion through down-regulation of thrombospondin-1

Cited by 20 publications

References 61 publications

Thrombospondin-1-derived 4N1K peptide expression is negatively associated with malignant aggressiveness and prognosis in urothelial carcinoma of the upper urinary tract

Thrombospondin-1-derived 4N1K peptide expression is negatively associated with malignant aggressiveness and prognosis in urothelial carcinoma of the upper urinary tract

Matricellular Protein Thrombospondins: Influence on Ocular Angiogenesis, Wound Healing and Immuneregulation

Claudin-7 inhibits human lung cancer cell migration and invasion through ERK/MAPK signaling pathway

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