CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in vivo and in vitro models

Schneiderhan, Wilhelm; Scheler, Mika; Kh, Holzmann; Marx, Maria; Gschwend, J. E.; Bucholz, M; Gress, Thomas M.; Seufferlein, Thomas; Adler, Guido; Oswald, Franz

doi:10.1136/gut.2009.181412

Cited by 145 publications

(113 citation statements)

References 45 publications

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“…Recently, it was demonstrated that expression and activity of MCT1 and MCT4 require co-expression of CD147 [3,4]. On the other hand, silencing studies showed that maturation and cell surface expression of CD147 depend on MCT1 and MCT4 expressions [3,17]. The present results show co-expression of CD147 with MCT1 and MCT4 in primary and metastatic EOC cells, supporting the concept that CD147 is an ancillary protein required for the expression of these MCTs [10].…”

Section: Discussionsupporting

confidence: 83%

“…Su et al [16] recently demonstrated that silencing of CD147 in A375 cells by a small interfering RNA (siRNA) clearly abrogated the expression of MCT1 and MCT4 and their co-localization with CD147 and dramatically decreased the glycolysis rate, extracellular pH, and the production of ATP. Using short hairpin RNA (shRNA) and RNAi technologies, Schneiderhan et al [17] further demonstrated that knock down of CD147 in MiaPaCa2 cells could inhibit the expression and function of MCT1 and MCT4 which result in an increased intracellular lactate concentration in vitro and in vivo animal model. However, expression profile of MCTs and the linkage among CD147, MCTs and MDR proteins in EOC are needed for further investigation.…”

Section: Introductionmentioning

confidence: 97%

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Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression

Chen

Wang

Beretov

et al. 2010

Clin Exp Metastasis

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Cancer metastasis and anti-cancer drug resistance are the major reason for the failure of clinical cancer treatment. We evaluated CD147, monocarboxylate transporters (MCT1 and MCT4), and multidrug resistance (MDR) markers (MDR1 and MRP2) in 4 epithelial ovarian cancer (EOC) cell lines and primary tumors (n = 120) along with the matched metastatic lesions (n = 40) with immunofluorescence labeling. We correlated CD147 with MCT1, MCT4, MDR1 and MRP2 markers in primary and metastatic cells in cell lines and tissues using confocal microscopy. We also investigated the relationship of expression of CD147, MCT1 and MCT4 with various progression parameters. Our results indicate that the co-expression of CD147 with MCTs or MDR markers was found in primary and metastatic EOC cells and stromal cells; the over-expression of CD147, MCT1 and MCT4 was found in most primary and the matched metastatic lesions of EOC, and was significantly associated with tumor stage, grade, residual disease status and presence of ascites (P < 0.05) but not with histology type (P > 0.05). These results suggest that over-expression of CD147, MCT1 and MCT4 is correlated with EOC progression, and co-expression of CD147 and MCT1/MCT4 is related to drug resistance during EOC metastasis and could be useful therapeutic targets to prevent the development of incurable, recurrent and drug resistance EOC.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 97%

Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression

Chen

Wang

Beretov

et al. 2010

Clin Exp Metastasis

View full text Add to dashboard Cite

show abstract

“…[18][19][20][21][22][23][24][25] However, patterns of MCT1 and MCT4 expression tend to vary among tumors, and currently, little is known about what regulates MCT1 and MCT4 expression. In general, MCT1 has been reported to be preferentially expressed in normoxic cells, while hypoxia-inducible MCT4 has been primarily reported to be expressed in glycolytic/hypoxic cells.…”

Section: Discussionmentioning

confidence: 99%

CD147 regulates the expression of MCT1 and lactate export in multiple myeloma cells

2013

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“…CD147 is a highly glycosylated transmembrane protein that regulates many protein families and that affects tumor invasiveness and metastasis [12,36,37]. MMP-9 and CD147 expression is associated with the malignant potential of pancreatic cancer cells [38], NSCLC cells [12] bladder cancer cells [13] and breast cancer cells [39]. Several lines of evidence have indicated that HO-1 induces tumor invasiveness and metastasis by regulating these metastasis-associated proteins [18,40].…”

Section: Introductionmentioning

confidence: 99%

High Glucose Promotes Tumor Invasion and Increases Metastasis-Associated Protein Expression in Human Lung Epithelial Cells by Upregulating Heme Oxygenase-1 via Reactive Oxygen Species or the TGF-β1/PI3K/Akt Signaling Pathway

Kang

Kong

et al. 2015

Cell Physiol Biochem

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Background: Growing evidence indicates that heme oxygenase-1 (HO-1) is up-regulated in malignancies and subsequently alters tumor aggressiveness and various cancer-related factors, such as high glucose (HG) levels. HO-1 expression can be induced when glucose concentrations are above 25 mM; however, the role of HO-1 in lung cancer patients with diabetes remains unknown. Therefore, in this study we investigated the promotion of tumor cell invasion and the expression of metastasis-associated proteins by inducing the up-regulation of HO-1 expression by HG treatment in A549 human lung epithelial cells. Methods: The expression of HO-1and metastasis-associated protein expression was explored by western blot analysis. HO-1 enzymatic activity, reactive oxygen species (ROS) production and TGF-β₁ production were examined by ELISA. Invasiveness was analyzed using a Transwell chamber. Results: HG treatment of A549 cells induced an increase in HO-1 expression, which was mediated by the HG-induced generation of reactive oxygen species (ROS) and transforming growth factor-β1 (TGF-β₁) in a concentration- and time-dependent manner. Following the increase in HO-1 expression, the enzymatic activity of HO-1 also increased in HG-treated cells. Pretreatment with N-acetyl-L-cysteine (NAC) or with phosphatidylinositol 3-kinase (PI3K)/Akt inhibitors attenuated the HG-induced increase in HO-1 expression. HG treatment of A549 cells enhanced the invasion potential of these cells, as shown with a Transwell assay, and increased metastasis-associated protein expression. However, HO-1 siRNA transfection significantly decreased these capabilities. Conclusion: this study is the first to demonstrate that HG treatment of A549 human lung epithelial cells promotes tumor cell invasion and increases metastasis-associated protein expression by up-regulating HO-1 expression via ROS or the TGF-β₁/PI3K/Akt signaling pathway.

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CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in vivo and in vitro models

Abstract: The function of CD147 as an ancillary protein that is required to sustain the expression and function of MCT1 and MCT4 is involved in the association of CD147 expression with the malignant potential of pancreatic cancer cells exhibiting the Warburg effect.

Cited by 145 publications

References 45 publications

Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression

Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression

CD147 regulates the expression of MCT1 and lactate export in multiple myeloma cells

High Glucose Promotes Tumor Invasion and Increases Metastasis-Associated Protein Expression in Human Lung Epithelial Cells by Upregulating Heme Oxygenase-1 via Reactive Oxygen Species or the TGF-β1/PI3K/Akt Signaling Pathway

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