Prognostic Value of Matrix Metalloproteinase-1/ Proteinase-Activated Receptor-1 Signaling Axis in Hepatocellular Carcinoma

Liao, Mingmei; Tong, Ping; Zhao, Jinfeng; Yang-de, Zhang; Li, Zhehai; Wang, Jiwei; Feng, Xueping; Hu, Man; Yi-feng, Pan

doi:10.1007/s12253-011-9458-8

Cited by 26 publications

(22 citation statements)

References 27 publications

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“…Tumorigenesis, angiogenesis, and experimental metastasis of several cancers can be inhibited effectively by pharmacologic blockade of PAR1 or knockdown of PAR1 gene expression (37, 39 -41). Recent work indicates that dual expression of MMP1 and PAR1 on cancer cells is significantly associated with increased tumor recurrence and stage in hepatocellular carcinoma patients and invasion and lymph node metastasis in primary gall bladder carcinoma (42,43).…”

Section: Matrix Metalloproteases (Mmps)mentioning

confidence: 99%

Matrix Metalloprotease-1a Promotes Tumorigenesis and Metastasis

Foley

Luo

O’Callaghan

et al. 2012

Journal of Biological Chemistry

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Background: Mmp1a is the postulated mouse genetic homologue of MMP1, but its functions in cancer are unknown. Results: Endogenous Mmp1a promotes invasion, tumorigenesis, and metastasis of lung cancer and melanoma. Conclusion: Mmp1a is a functional MMP1 homologue in mouse models of tumorigenesis. Significance: This is the first report that directly characterizes a function for Mmp1a in mouse (patho)physiology.

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Section: Matrix Metalloproteases (Mmps)mentioning

confidence: 99%

Matrix Metalloprotease-1a Promotes Tumorigenesis and Metastasis

Foley

Luo

O’Callaghan

et al. 2012

Journal of Biological Chemistry

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“…MMPs contribute to the regulation of cancer cell invasion and tumor metastasis [26–30]. Expression of various MMPs including MMP-1, MMP-2, MMP-9, MMP-12 and MMP-14 were implicated in regulating HCC tumor progression and prognosis [31–40]. In this study, we found that HCC-secreted 14-3-3σ stimulates MMP expression in cancer-associated cells.…”

Section: Introductionmentioning

confidence: 62%

“…Elevated MMP-1, MMP-2, MMP-9, MMP-12 and MMP-14 expression are correlated with clinical significance of HCC [31–40]. Intriguingly, moderate levels of membrane type 1-MMP and MMP-9 were detected in cancer and stromal cells.…”

Section: Discussionmentioning

confidence: 99%

Paracrine regulation of matrix metalloproteinases contributes to cancer cell invasion by hepatocellular carcinoma-secreted 14-3-3σ

et al. 2016

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14-3-3σ overexpression results in enhanced hepatocellular carcinoma (HCC) cell migration and HCC tumor vascular-invasion is significantly associated with 14-3-3σ expression. However, increased expression of 14-3-3σ paradoxically suppresses in vitro cell invasion of HCC. We hypothesize that surrounding tumor-associated stromal cells play a crucial role in 14-3-3σ-regulated HCC cell invasion. In this study, H68 fibroblasts, THP-1 and phorbol-12-myristate-13-acetate (PMA)-treated THP-1 (PMA-THP-1) cells were incubated with conditioned media of control (control-CM) and 14-3-3σ-overepxressing cells (14-3-3σ-CM), followed by co-culture with HCC cells. Invasiveness of HCC cells was examined by a Boyden chamber assay. HCC cells co-cultured with 14-3-3σ-CM treated cells significantly enhanced their invasive ability compared with control-CM treated cells. Moreover, incubation with 14-3-3σ-CM induced differential expression profiles of matrix metalloproteinases (MMPs) in fibroblasts (MMP-1, MMP-2, MMP-9, MMP-12 and MMP-14), THP-1 (MMP-1 and MMP-12) and PMA-THP-1 cells (MMP-2, MMP-12 and MMP-14). In contrast, silencing of 14-3-3σ by siRNA significantly abolished 14-3-3σ-CM induced MMPs. In addition, treatment with recombinant 14-3-3σ (r14-3-3σ) protein exhibits a similar expression profile of MMPs induced by 14-3-3σ-CM in fibroblasts, THP-1 and PMA-THP-1 cells. Finally, knockdown of aminopeptidase N (APN) significantly abrogated r14-3-3σ induced expression of MMPs in HS68 fibroblasts. These results suggest that HCC-secreted 14-3-3σ promotes expression of MMPs in cancerous surrounding cells via an APN dependent mechanism. 14-3-3σ has a paracrine effect in educating stromal cells in tumor-associated microenvironment.

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“…The matrix metalloproteinase-1 (MMP-1) and protease activated receptor-1 (PAR-1) are expressed in HCC but not in normal liver. The up-regulation of MMP-1/PAR-1 axis has prognostic value [20] and potentially could be used in the identification of malignancy. Co-expression of stem cell transcription factors Oct4 and Nanog indicates aggressive tumour behaviour and predicts recurrence after HCC resection [22].…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

“…IHC is mandatory for the diagnostics of haematological neoplasms and epithelioid haemangioendothelioma. Assessment of tumour biological potential can be done by IHC, evaluating Ki-67, Cyclin D1, FOXJ1, stem cell markers, matrix metalloproteinases and other markers [7][8][18][19][20][21][22]. Novel markers appear continuously as heat-shock protein 70 [23].…”

mentioning

confidence: 99%