Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive Phenotype

Colorectal cancer (CRC) is the third most common cancer in the world and represents the third most deadly tumor worldwide. About 15–25% of patients present metastasis in the moment of diagnosis, the liver being the most common site of metastization. Therefore, the development of new therapeutic agen...

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Main Authors: Cristina Almeida, Ana Luísa Teixeira, Francisca Dias, Vera Machado, Mariana Morais, Gabriela Martins, Carlos Palmeira, Maria Emília Sousa, Inês Godinho, Sílvia Batista, Bruno Costa-Silva, Rui Medeiros
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/11/1/145
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author Cristina Almeida
Ana Luísa Teixeira
Francisca Dias
Vera Machado
Mariana Morais
Gabriela Martins
Carlos Palmeira
Maria Emília Sousa
Inês Godinho
Sílvia Batista
Bruno Costa-Silva
Rui Medeiros
author_facet Cristina Almeida
Ana Luísa Teixeira
Francisca Dias
Vera Machado
Mariana Morais
Gabriela Martins
Carlos Palmeira
Maria Emília Sousa
Inês Godinho
Sílvia Batista
Bruno Costa-Silva
Rui Medeiros
author_sort Cristina Almeida
collection DOAJ
description Colorectal cancer (CRC) is the third most common cancer in the world and represents the third most deadly tumor worldwide. About 15–25% of patients present metastasis in the moment of diagnosis, the liver being the most common site of metastization. Therefore, the development of new therapeutic agents is needed, to improve the patients’ prognosis. Amino acids transporters, LAT1 and ASCT2, are described as upregulated in CRC, being associated with a poor prognosis. Extracellular vesicles have emerged as key players in cell-to-cell communication due to their ability to transfer biomolecules between cells, with a phenotypic impact on the recipient cells. Thus, this study analyzes the presence of <i>LAT1</i> and <i>ASCT2</i> mRNAs in CRC-EVs and evaluates their role in phenotype modulation in a panel of four recipient cell lines (HCA-7, HEPG-2, SK-HEP-1, HKC-8). We found that HCT 116-EVs carry <i>LAT1</i>, <i>ASCT2</i> and other oncogenic mRNAs being taken up by recipient cells. Moreover, the HCT 116-EVs’ internalization was associated with the increase of <i>LAT1</i> mRNA in SK-HEP-1 cells. We also observed that HCT 116-EVs induce a higher cell migration capacity and proliferation of SK-HEP-1 and HKC-8 cells. The present study supports the <i>LAT1</i>-EVs’ mRNA involvement in cell phenotype modulation, conferring advantages in cell migration and proliferation.
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spelling doaj.art-58470b97cf64477bb9c25f297703fabf2023-11-23T13:01:58ZengMDPI AGBiology2079-77372022-01-0111114510.3390/biology11010145Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive PhenotypeCristina Almeida0Ana Luísa Teixeira1Francisca Dias2Vera Machado3Mariana Morais4Gabriela Martins5Carlos Palmeira6Maria Emília Sousa7Inês Godinho8Sílvia Batista9Bruno Costa-Silva10Rui Medeiros11Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalMolecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalMolecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalMolecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalMolecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalImmunology Department, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalImmunology Department, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalImmunology Department, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalImmunology Department, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalSystems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisbon, PortugalSystems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisbon, PortugalMolecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, PortugalColorectal cancer (CRC) is the third most common cancer in the world and represents the third most deadly tumor worldwide. About 15–25% of patients present metastasis in the moment of diagnosis, the liver being the most common site of metastization. Therefore, the development of new therapeutic agents is needed, to improve the patients’ prognosis. Amino acids transporters, LAT1 and ASCT2, are described as upregulated in CRC, being associated with a poor prognosis. Extracellular vesicles have emerged as key players in cell-to-cell communication due to their ability to transfer biomolecules between cells, with a phenotypic impact on the recipient cells. Thus, this study analyzes the presence of <i>LAT1</i> and <i>ASCT2</i> mRNAs in CRC-EVs and evaluates their role in phenotype modulation in a panel of four recipient cell lines (HCA-7, HEPG-2, SK-HEP-1, HKC-8). We found that HCT 116-EVs carry <i>LAT1</i>, <i>ASCT2</i> and other oncogenic mRNAs being taken up by recipient cells. Moreover, the HCT 116-EVs’ internalization was associated with the increase of <i>LAT1</i> mRNA in SK-HEP-1 cells. We also observed that HCT 116-EVs induce a higher cell migration capacity and proliferation of SK-HEP-1 and HKC-8 cells. The present study supports the <i>LAT1</i>-EVs’ mRNA involvement in cell phenotype modulation, conferring advantages in cell migration and proliferation.https://www.mdpi.com/2079-7737/11/1/145colorectal cancer (CRC)mRNAsLAT1ASCT2extracellular vesicles (EV’s)
spellingShingle Cristina Almeida
Ana Luísa Teixeira
Francisca Dias
Vera Machado
Mariana Morais
Gabriela Martins
Carlos Palmeira
Maria Emília Sousa
Inês Godinho
Sílvia Batista
Bruno Costa-Silva
Rui Medeiros
Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive Phenotype
Biology
colorectal cancer (CRC)
mRNAs
LAT1
ASCT2
extracellular vesicles (EV’s)
title Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive Phenotype
title_full Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive Phenotype
title_fullStr Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive Phenotype
title_full_unstemmed Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive Phenotype
title_short Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive Phenotype
title_sort extracellular vesicles derived lat1 mrna as a powerful inducer of colorectal cancer aggressive phenotype
topic colorectal cancer (CRC)
mRNAs
LAT1
ASCT2
extracellular vesicles (EV’s)
url https://www.mdpi.com/2079-7737/11/1/145
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