Peptides against Low Density Lipoprotein (LDL) Aggregation Inhibit Intracellular Cholesteryl Ester Loading and Proliferation of Pancreatic Tumor Cells
Dyslipidemia, metabolic disorders and/or obesity are postulated as risk factors for pancreatic ductal adenocarcinoma (PDAC). The majority of patients with these metabolic alterations have low density lipoproteins (LDLs) with increased susceptibility to become aggregated in the extracellular matrix (...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/4/890 |
| _version_ | 1797482087084720128 |
|---|---|
| author | Aleyda Benitez-Amaro Neus Martínez-Bosch Noemí Manero-Rupérez Lene Claudi Maria Teresa La Chica Lhoëst Marta Soler Lia Ros-Blanco Pilar Navarro Vicenta Llorente-Cortés |
| author_facet | Aleyda Benitez-Amaro Neus Martínez-Bosch Noemí Manero-Rupérez Lene Claudi Maria Teresa La Chica Lhoëst Marta Soler Lia Ros-Blanco Pilar Navarro Vicenta Llorente-Cortés |
| author_sort | Aleyda Benitez-Amaro |
| collection | DOAJ |
| description | Dyslipidemia, metabolic disorders and/or obesity are postulated as risk factors for pancreatic ductal adenocarcinoma (PDAC). The majority of patients with these metabolic alterations have low density lipoproteins (LDLs) with increased susceptibility to become aggregated in the extracellular matrix (ECM). LDL aggregation can be efficiently inhibited by low-density lipoprotein receptor-related protein 1 (LRP1)-based peptides. The objectives of this work were: (i) to determine if aggregated LDLs affect the intracellular cholesteryl ester (CE)/free cholesterol (FC) ratio and/or the tumor pancreatic cell proliferation, using sphingomyelinase-modified LDL particles (Aggregated LDL, AgLDL); and (ii) to test whether LRP1-based peptides, highly efficient against LDL aggregation, can interfere in these processes. For this, we exposed human pancreatic cancer cell lines (PANC-1, RWP-1 and Capan-1) to native (nLDL) or AgLDLs in the absence or presence of LRP1-based peptides (DP3) or irrelevant peptides (IP321). Results of thin-layer chromatography (TLC) following lipid extraction indicate that AgLDLs induce a higher intracellular CE/FC ratio than nLDL, and that DP3 but not IP321 counteracts this effect. AgLDLs also increase PANC-1 cell proliferation, which is inhibited by the DP3 peptide. Our results indicate that AgLDL-induced intracellular CE accumulation plays a crucial role in the proliferation of pancreatic tumor cell lines. Peptides with anti-LDL aggregation properties may thus exhibit anti-tumor effects. |
| first_indexed | 2024-03-09T22:25:14Z |
| format | Article |
| id | doaj.art-989a6238570a4d61bacd0d91a94ab996 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:25:14Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-989a6238570a4d61bacd0d91a94ab9962023-11-23T19:08:02ZengMDPI AGCancers2072-66942022-02-0114489010.3390/cancers14040890Peptides against Low Density Lipoprotein (LDL) Aggregation Inhibit Intracellular Cholesteryl Ester Loading and Proliferation of Pancreatic Tumor CellsAleyda Benitez-Amaro0Neus Martínez-Bosch1Noemí Manero-Rupérez2Lene Claudi3Maria Teresa La Chica Lhoëst4Marta Soler5Lia Ros-Blanco6Pilar Navarro7Vicenta Llorente-Cortés8Institute of Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, SpainCancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Unidad Asociada IIBB-CSIC, 08003 Barcelona, SpainCancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Unidad Asociada IIBB-CSIC, 08003 Barcelona, SpainInstitute of Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, SpainInstitute of Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, SpainBiomedical Research Institute Sant Pau (IIB Sant Pau), 08025 Barcelona, SpainBiomedical Research Institute Sant Pau (IIB Sant Pau), 08025 Barcelona, SpainInstitute of Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, SpainInstitute of Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, SpainDyslipidemia, metabolic disorders and/or obesity are postulated as risk factors for pancreatic ductal adenocarcinoma (PDAC). The majority of patients with these metabolic alterations have low density lipoproteins (LDLs) with increased susceptibility to become aggregated in the extracellular matrix (ECM). LDL aggregation can be efficiently inhibited by low-density lipoprotein receptor-related protein 1 (LRP1)-based peptides. The objectives of this work were: (i) to determine if aggregated LDLs affect the intracellular cholesteryl ester (CE)/free cholesterol (FC) ratio and/or the tumor pancreatic cell proliferation, using sphingomyelinase-modified LDL particles (Aggregated LDL, AgLDL); and (ii) to test whether LRP1-based peptides, highly efficient against LDL aggregation, can interfere in these processes. For this, we exposed human pancreatic cancer cell lines (PANC-1, RWP-1 and Capan-1) to native (nLDL) or AgLDLs in the absence or presence of LRP1-based peptides (DP3) or irrelevant peptides (IP321). Results of thin-layer chromatography (TLC) following lipid extraction indicate that AgLDLs induce a higher intracellular CE/FC ratio than nLDL, and that DP3 but not IP321 counteracts this effect. AgLDLs also increase PANC-1 cell proliferation, which is inhibited by the DP3 peptide. Our results indicate that AgLDL-induced intracellular CE accumulation plays a crucial role in the proliferation of pancreatic tumor cell lines. Peptides with anti-LDL aggregation properties may thus exhibit anti-tumor effects.https://www.mdpi.com/2072-6694/14/4/890anti-LDL aggregation peptidesLDL atherogenicitycholesteryl esterspancreatic ductal adenocarcinoma |
| spellingShingle | Aleyda Benitez-Amaro Neus Martínez-Bosch Noemí Manero-Rupérez Lene Claudi Maria Teresa La Chica Lhoëst Marta Soler Lia Ros-Blanco Pilar Navarro Vicenta Llorente-Cortés Peptides against Low Density Lipoprotein (LDL) Aggregation Inhibit Intracellular Cholesteryl Ester Loading and Proliferation of Pancreatic Tumor Cells Cancers anti-LDL aggregation peptides LDL atherogenicity cholesteryl esters pancreatic ductal adenocarcinoma |
| title | Peptides against Low Density Lipoprotein (LDL) Aggregation Inhibit Intracellular Cholesteryl Ester Loading and Proliferation of Pancreatic Tumor Cells |
| title_full | Peptides against Low Density Lipoprotein (LDL) Aggregation Inhibit Intracellular Cholesteryl Ester Loading and Proliferation of Pancreatic Tumor Cells |
| title_fullStr | Peptides against Low Density Lipoprotein (LDL) Aggregation Inhibit Intracellular Cholesteryl Ester Loading and Proliferation of Pancreatic Tumor Cells |
| title_full_unstemmed | Peptides against Low Density Lipoprotein (LDL) Aggregation Inhibit Intracellular Cholesteryl Ester Loading and Proliferation of Pancreatic Tumor Cells |
| title_short | Peptides against Low Density Lipoprotein (LDL) Aggregation Inhibit Intracellular Cholesteryl Ester Loading and Proliferation of Pancreatic Tumor Cells |
| title_sort | peptides against low density lipoprotein ldl aggregation inhibit intracellular cholesteryl ester loading and proliferation of pancreatic tumor cells |
| topic | anti-LDL aggregation peptides LDL atherogenicity cholesteryl esters pancreatic ductal adenocarcinoma |
| url | https://www.mdpi.com/2072-6694/14/4/890 |
| work_keys_str_mv | AT aleydabenitezamaro peptidesagainstlowdensitylipoproteinldlaggregationinhibitintracellularcholesterylesterloadingandproliferationofpancreatictumorcells AT neusmartinezbosch peptidesagainstlowdensitylipoproteinldlaggregationinhibitintracellularcholesterylesterloadingandproliferationofpancreatictumorcells AT noemimaneroruperez peptidesagainstlowdensitylipoproteinldlaggregationinhibitintracellularcholesterylesterloadingandproliferationofpancreatictumorcells AT leneclaudi peptidesagainstlowdensitylipoproteinldlaggregationinhibitintracellularcholesterylesterloadingandproliferationofpancreatictumorcells AT mariateresalachicalhoest peptidesagainstlowdensitylipoproteinldlaggregationinhibitintracellularcholesterylesterloadingandproliferationofpancreatictumorcells AT martasoler peptidesagainstlowdensitylipoproteinldlaggregationinhibitintracellularcholesterylesterloadingandproliferationofpancreatictumorcells AT liarosblanco peptidesagainstlowdensitylipoproteinldlaggregationinhibitintracellularcholesterylesterloadingandproliferationofpancreatictumorcells AT pilarnavarro peptidesagainstlowdensitylipoproteinldlaggregationinhibitintracellularcholesterylesterloadingandproliferationofpancreatictumorcells AT vicentallorentecortes peptidesagainstlowdensitylipoproteinldlaggregationinhibitintracellularcholesterylesterloadingandproliferationofpancreatictumorcells |