Monocarboxylate transporters MCT1 and MCT4 regulate migration and invasion of pancreatic ductal adenocarcinoma cells

Research output: Contribution to journal › Journal article › Research › peer-review

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Monocarboxylate transporters MCT1 and MCT4 regulate migration and invasion of pancreatic ductal adenocarcinoma cells. / Kong, Su Chii; Nøhr-Nielsen, Asbjørn; Zeeberg, Katrine; Reshkin, Stephan Joel; Hoffmann, Else Kay; Novak, Ivana; Pedersen, Stine Helene Falsig.

In: Pancreas, Vol. 45, No. 7, 2016, p. 1036-1047.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kong, SC, Nøhr-Nielsen, A, Zeeberg, K, Reshkin, SJ, Hoffmann, EK, Novak, I & Pedersen, SHF 2016, 'Monocarboxylate transporters MCT1 and MCT4 regulate migration and invasion of pancreatic ductal adenocarcinoma cells', Pancreas, vol. 45, no. 7, pp. 1036-1047. https://doi.org/10.1097/MPA.0000000000000571

APA

Kong, S. C., Nøhr-Nielsen, A., Zeeberg, K., Reshkin, S. J., Hoffmann, E. K., Novak, I., & Pedersen, S. H. F. (2016). Monocarboxylate transporters MCT1 and MCT4 regulate migration and invasion of pancreatic ductal adenocarcinoma cells. Pancreas, 45(7), 1036-1047. https://doi.org/10.1097/MPA.0000000000000571

Vancouver

Kong SC, Nøhr-Nielsen A, Zeeberg K, Reshkin SJ, Hoffmann EK, Novak I et al. Monocarboxylate transporters MCT1 and MCT4 regulate migration and invasion of pancreatic ductal adenocarcinoma cells. Pancreas. 2016;45(7):1036-1047. https://doi.org/10.1097/MPA.0000000000000571

Author

Kong, Su Chii ; Nøhr-Nielsen, Asbjørn ; Zeeberg, Katrine ; Reshkin, Stephan Joel ; Hoffmann, Else Kay ; Novak, Ivana ; Pedersen, Stine Helene Falsig. / Monocarboxylate transporters MCT1 and MCT4 regulate migration and invasion of pancreatic ductal adenocarcinoma cells. In: Pancreas. 2016 ; Vol. 45, No. 7. pp. 1036-1047.

Bibtex

@article{3f35378020bd4f2a8580d4de063e0bef,
title = "Monocarboxylate transporters MCT1 and MCT4 regulate migration and invasion of pancreatic ductal adenocarcinoma cells",
abstract = "OBJECTIVES: Novel treatments for pancreatic ductal adenocarcinoma (PDAC) are severely needed. The aim of this work was to explore the roles of H-lactate monocarboxylate transporters 1 and 4 (MCT1 and MCT4) in PDAC cell migration and invasiveness. METHODS: Monocarboxylate transporter expression, localization, activity, and function were explored in human PDAC cells (MIAPaCa-2, Panc-1, BxPC-3, AsPC-1) and normal human pancreatic ductal epithelial (HPDE) cells, by quantitative polymerase chain reaction, immunoblotting, immunocytochemistry, lactate flux, migration, and invasion assays. RESULTS: MCT1 and MCT4 (messenger RNA, protein) were robustly expressed in all PDAC lines, localizing to the plasma membrane. Lactate influx capacity was highest in AsPC-1 cells and lowest in HPDE cells and was inhibited by the MCT inhibitor α-cyano-4-hydroxycinnamate (4-CIN), MCT1/MCT2 inhibitor AR-C155858, or knockdown of MCT1 or MCT4. PDAC cell migration was largely unaffected by MCT1/MCT2 inhibition or MCT1 knockdown but was reduced by 4-CIN and by MCT4 knockdown (BxPC-3). Invasion measured in Boyden chamber (BxPC-3, Panc-1) and spheroid outgrowth (BxPC-3) assays was attenuated by 4-CIN and AR-C155858 and by MCT1 or MCT4 knockdown. CONCLUSIONS: Human PDAC cells exhibit robust MCT1 and MCT4 expression and partially MCT1- and MCT4-dependent lactate flux. PDAC cell migration is partially dependent on MCT4; and invasion, on MCT1 and MCT4. Inhibition of MCT1 and MCT4 may have clinical relevance in PDAC.",
author = "Kong, {Su Chii} and Asbj{\o}rn N{\o}hr-Nielsen and Katrine Zeeberg and Reshkin, {Stephan Joel} and Hoffmann, {Else Kay} and Ivana Novak and Pedersen, {Stine Helene Falsig}",
year = "2016",
doi = "10.1097/MPA.0000000000000571",
language = "English",
volume = "45",
pages = "1036--1047",
journal = "Pancreas",
issn = "0885-3177",
publisher = "Lippincott Williams & Wilkins",
number = "7",

}

RIS

TY - JOUR

T1 - Monocarboxylate transporters MCT1 and MCT4 regulate migration and invasion of pancreatic ductal adenocarcinoma cells

AU - Kong, Su Chii

AU - Nøhr-Nielsen, Asbjørn

AU - Zeeberg, Katrine

AU - Reshkin, Stephan Joel

AU - Hoffmann, Else Kay

AU - Novak, Ivana

AU - Pedersen, Stine Helene Falsig

PY - 2016

Y1 - 2016

N2 - OBJECTIVES: Novel treatments for pancreatic ductal adenocarcinoma (PDAC) are severely needed. The aim of this work was to explore the roles of H-lactate monocarboxylate transporters 1 and 4 (MCT1 and MCT4) in PDAC cell migration and invasiveness. METHODS: Monocarboxylate transporter expression, localization, activity, and function were explored in human PDAC cells (MIAPaCa-2, Panc-1, BxPC-3, AsPC-1) and normal human pancreatic ductal epithelial (HPDE) cells, by quantitative polymerase chain reaction, immunoblotting, immunocytochemistry, lactate flux, migration, and invasion assays. RESULTS: MCT1 and MCT4 (messenger RNA, protein) were robustly expressed in all PDAC lines, localizing to the plasma membrane. Lactate influx capacity was highest in AsPC-1 cells and lowest in HPDE cells and was inhibited by the MCT inhibitor α-cyano-4-hydroxycinnamate (4-CIN), MCT1/MCT2 inhibitor AR-C155858, or knockdown of MCT1 or MCT4. PDAC cell migration was largely unaffected by MCT1/MCT2 inhibition or MCT1 knockdown but was reduced by 4-CIN and by MCT4 knockdown (BxPC-3). Invasion measured in Boyden chamber (BxPC-3, Panc-1) and spheroid outgrowth (BxPC-3) assays was attenuated by 4-CIN and AR-C155858 and by MCT1 or MCT4 knockdown. CONCLUSIONS: Human PDAC cells exhibit robust MCT1 and MCT4 expression and partially MCT1- and MCT4-dependent lactate flux. PDAC cell migration is partially dependent on MCT4; and invasion, on MCT1 and MCT4. Inhibition of MCT1 and MCT4 may have clinical relevance in PDAC.

AB - OBJECTIVES: Novel treatments for pancreatic ductal adenocarcinoma (PDAC) are severely needed. The aim of this work was to explore the roles of H-lactate monocarboxylate transporters 1 and 4 (MCT1 and MCT4) in PDAC cell migration and invasiveness. METHODS: Monocarboxylate transporter expression, localization, activity, and function were explored in human PDAC cells (MIAPaCa-2, Panc-1, BxPC-3, AsPC-1) and normal human pancreatic ductal epithelial (HPDE) cells, by quantitative polymerase chain reaction, immunoblotting, immunocytochemistry, lactate flux, migration, and invasion assays. RESULTS: MCT1 and MCT4 (messenger RNA, protein) were robustly expressed in all PDAC lines, localizing to the plasma membrane. Lactate influx capacity was highest in AsPC-1 cells and lowest in HPDE cells and was inhibited by the MCT inhibitor α-cyano-4-hydroxycinnamate (4-CIN), MCT1/MCT2 inhibitor AR-C155858, or knockdown of MCT1 or MCT4. PDAC cell migration was largely unaffected by MCT1/MCT2 inhibition or MCT1 knockdown but was reduced by 4-CIN and by MCT4 knockdown (BxPC-3). Invasion measured in Boyden chamber (BxPC-3, Panc-1) and spheroid outgrowth (BxPC-3) assays was attenuated by 4-CIN and AR-C155858 and by MCT1 or MCT4 knockdown. CONCLUSIONS: Human PDAC cells exhibit robust MCT1 and MCT4 expression and partially MCT1- and MCT4-dependent lactate flux. PDAC cell migration is partially dependent on MCT4; and invasion, on MCT1 and MCT4. Inhibition of MCT1 and MCT4 may have clinical relevance in PDAC.

U2 - 10.1097/MPA.0000000000000571

DO - 10.1097/MPA.0000000000000571

M3 - Journal article

C2 - 26765963

AN - SCOPUS:84954350066

VL - 45

SP - 1036

EP - 1047

JO - Pancreas

JF - Pancreas

SN - 0885-3177

IS - 7

ER -

ID: 161239524