Silencing of CD44 by siRNA suppressed invasion, migration and adhesion to matrix, but not secretion of MMPs, of cholangiocarcinoma cells

Pongcharoen, Pongsanat; Jinawath, Artit; Tohtong, Rutaiwan

doi:10.1007/s10585-011-9414-8

Cited by 23 publications

(21 citation statements)

References 42 publications

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“…Gelatinase activity of MMP-2 was assessed using gelatin zymography as previously described [26]. C33A stably expressing different oncoproteins were incubated in serum-free medium for 48 h before analysis.…”

Section: Methodsmentioning

confidence: 99%

HPV16 Oncoproteins Promote Cervical Cancer Invasiveness by Upregulating Specific Matrix Metalloproteinases

et al. 2013

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Production of matrix metalloproteinases (MMPs) for degradation of extracellular matrix is a vital step in cancer metastasis. We investigated the effects of HPV16 oncoproteins (16E6, 16E6*I and 16E7), either individually or combined, on the transcription of 7 MMPs implicated in cervical cancer invasiveness. The levels of 7 MMPs reported to be increased in cervical cancer were determined in C33A stably expressing different HPV16 oncoproteins using quantitative RT-PCR and compared with invasion ability of cell lines using in vitro invasion and wound healing assays. Overexpression of MMP-2 and MT1-MMP was detected in HPV16E6E7 expressing cells which correlated with increased cell invasion. Combination of HPV oncoproteins always showed greater effects than its individual form. Inhibition of cell invasion using a specific MMP-2 inhibitor, OA-Hy, and anti-MT1-MMP antibody confirmed that invasion in these cells was dependent on both MMP-2 and MT1-MMP expression. Depletion of HPV16E6E7 by shRNA-mediated knock-down experiments resulted in decreased MMP-2 and MT1-MMP expression levels as well as reduced invasion ability which strongly suggested specific effects of HPV oncoproteins on both MMPs and on cell invasion. Immunohistochemistry study in invasive cervical cancers confirmed the enhanced in vivo expression of these two MMPs in HPV16-infected cells. In addition, possible sites required by HPV16E6E7 on the MMP-2 and MT1-MMP promoters were investigated and PEA3 (at −552/−540 for MMP-2, −303 for MT1-MMP) and Sp1 (at −91 for MMP-2, −102 for MT1-MMP) binding sites were shown to be essential for mediating their transactivation activity. In conclusion, our study demonstrated that HPV16E6 and E7 oncoproteins cooperate in promoting cervical cancer invasiveness by specifically upregulating MMP-2 and MT1-MMP transcription in a similar manner.

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Section: Methodsmentioning

confidence: 99%

HPV16 Oncoproteins Promote Cervical Cancer Invasiveness by Upregulating Specific Matrix Metalloproteinases

et al. 2013

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“…In addition, the RNA interference-based blockage of EpCAM in hepatic stem/progenitor cells induced a decrease in tumorigenicity and invasiveness [34,61]. Recent studies also revealed that CD44 silencing by siRNA has a significant effect on invasiveness, migration, and adhesion in cholangiocarcinoma cell lines [62]. Moreover, CD24 inhibition using siRNA significantly decreased the invasive capacity of cholangiocarcinoma cells [28].…”

Section: A Possible Targeted Therapy For Cholangiocarcinoma Stem Cellsmentioning

confidence: 99%

Recent advances in cancer stem cell research for cholangiocarcinoma

Kokuryo

Yokoyama

Nagino

2012

J Hepato Biliary Pancreat

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Cancer stem cells have been identified as cells with the capacity to self‐renew and differentiate into multiple lineages of human malignancies. Cholangiocarcinoma is one of the most difficult intra‐abdominal malignancies that can be treated using a surgical approach. Chemotherapy in addition to surgery is necessary to improve patient survival. However, its clinical benefit is limited, and, to date, no other effective anticancer drug is available for this disease. Several reports have shown the existence of cholangiocarcinoma stem cells. Cell surface antigens such as CD133, CD24, EpCAM, CD44, and others have been used to isolate cholangiocarcinoma stem cells. In general, enhanced expression of these markers in resected specimens of cholangiocarcinoma was associated with malignant potential. Distinct and specific pathways are expected to be present in cancer stem cells compared to other cancer cells that have no stem cell properties. To date, reports showing possible signaling pathways in cholangiocarcinoma stem cells are limited. More research is anticipated. Targeting therapies for surface molecular markers or specific signaling pathways of cholangiocarcinoma stem cells may be important in order to change the clinical outcome of patients with this disease. However, no clinical trial has been performed so far. This review will focus on the markers and signaling pathways used to define cholangiocarcinoma stem cells. A novel therapeutic approach of targeting cholangiocarcinoma stem cells will also be discussed.

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“…Cancer stem cells, which possess stem cell‐like characteristics, including multilineage and self‐renewal potentials, have been identified in cancer tissues . Previous studies reported that tumor progression, metastasis, and resistance to anticancer therapy were driven by CSCs, which were identified by cell surface markers such as CD44 . CD44 exists in numerous variant isoforms generated through the alternative mRNA splicing of different combinations of 10 exons (v1‐10), and the variant isoforms of CD44 containing v8‐v10 (CD44v9) have been identified as new cell surface markers of CSCs .…”

Section: Introductionmentioning

confidence: 99%

Sulfasalazine could modulate the CD44v9‐xCT system and enhance cisplatin‐induced cytotoxic effects in metastatic bladder cancer

et al. 2019

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The prognostic role of CD 44v9, a variant isoform of CD 44 and a new cell surface marker of cancer stem cells, remains unclear in bladder cancer ( BC ) patients. Furthermore, limited information is available on the functional role of sulfasalazine ( SSZ ), which could modulate the CD 44v9‐ xCT system in order to enhance cisplatin ( CDDP )‐induced cytotoxicity and inhibit the metastatic potential of BC . CD 44v9 protein expression was examined immunohistochemically in 63 muscle invasive BC ( MIBC ) patients who underwent radical cystectomy. CD 44v9 expression was independently associated with disease recurrence and cancer‐specific death in MIBC . Cytotoxic effects, glutathione levels, and reactive oxygen species production by SSZ and CD 44v9 and phospho‐p38 MAPK protein expression by SSZ with or without CDDP were assessed in MBT ‐2V cells with highly metastatic potential. Sulfasalazine exerted cytotoxic effects against MBT ‐2V cells by inhibiting glutathione levels and inducing the production of reactive oxygen species. Sulfasalazine in combination with CDDP appeared to exert strong cytotoxic effects against MBT ‐2V cells by inhibiting CD 44v9 expression and upregulating phospho‐p38 MAPK expression. The inhibitory effects of SSZ with or without CDDP were also investigated using an MBT ‐2V lung metastatic model. In the murine lung metastatic BC model, SSZ significantly prolonged animal survival. Furthermore, the combination of SSZ with CDDP exerted stronger inhibitory effects on the establishment of lung tumor nodules than SSZ or CDDP alone. CD 44v9 expression could be a clinical biomarker for predicting poor outcomes in MIBC patients. Sulfasalazine in combination with CDDP has potential as a novel therapy against metastatic BC .

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Silencing of CD44 by siRNA suppressed invasion, migration and adhesion to matrix, but not secretion of MMPs, of cholangiocarcinoma cells

Cited by 23 publications

References 42 publications

HPV16 Oncoproteins Promote Cervical Cancer Invasiveness by Upregulating Specific Matrix Metalloproteinases

HPV16 Oncoproteins Promote Cervical Cancer Invasiveness by Upregulating Specific Matrix Metalloproteinases

Recent advances in cancer stem cell research for cholangiocarcinoma

Sulfasalazine could modulate the CD44v9‐xCT system and enhance cisplatin‐induced cytotoxic effects in metastatic bladder cancer

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