CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in vivo and in vitro models
- W Schneiderhan 1, M Scheler , K-H Holzmann , M Marx , J E Gschwend , M Bucholz , T M Gress , T Seufferlein , G Adler , F Oswald
- 1Institute for Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, Franz-Josef-Strauss Allee 11, D-93053 Regensburg, Germany. wilhelm.schneiderhan@klinik.uni-regensburg.de
- 0Institute for Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, Franz-Josef-Strauss Allee 11, D-93053 Regensburg, Germany. wilhelm.schneiderhan@klinik.uni-regensburg.de
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View abstract on PubMed
Summary
This summary is machine-generated.CD147 glycoprotein is crucial for pancreatic cancer cell growth and lactate transport via MCT1 and MCT4. Silencing CD147 inhibits proliferation, invasion, and tumor growth, highlighting its role in the Warburg effect.
Area Of Science
- Oncology
- Molecular Biology
- Biochemistry
Background
- CD147 (basigin, EMMPRIN) is a glycoprotein found in pancreatic ductal adenocarcinomas (PDACs), linked to poor prognosis.
- Its specific role in pancreatic cancer progression was previously unclear.
Purpose Of The Study
- To investigate the function of CD147 in pancreatic cancer.
- To determine the relationship between CD147, monocarboxylate transporters (MCTs), and the Warburg effect.
Main Methods
- RNA interference (RNAi) and short hairpin RNA (shRNA) were used to silence CD147 in pancreatic cancer cell lines (MiaPaCa2, Panc1).
- Real-time RT-PCR and immunohistology assessed MCT1 and MCT4 expression.
- In vitro proliferation and lactate production assays were performed.
- In vivo studies included chick embryo chorioallantoic membrane (CAM) invasion assays and nude mouse xenograft models.
Main Results
- CD147 silencing reduced pancreatic cancer cell proliferation and lactate production.
- CD147 is essential for the expression and function of monocarboxylate transporters MCT1 and MCT4.
- Inhibition of CD147 led to increased intracellular lactate and decreased cancer cell growth when exogenous lactate was added.
- CD147 knockdown reduced tumor invasiveness and tumorigenicity in vivo.
Conclusions
- CD147 acts as an ancillary protein supporting MCT1 and MCT4 expression and function.
- CD147 contributes to the malignant potential of pancreatic cancer cells by influencing the Warburg effect.
- Targeting CD147 may represent a therapeutic strategy for pancreatic cancer.
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