TY - JOUR
T1 - Lung Tumor Cells with Different Tn Antigen Expression Present Distinctive Immunomodulatory Properties
AU - Costa, Valeria da
AU - Mariño, Karina V.
AU - Rodríguez-Zraquia, Santiago A.
AU - Festari, María Florencia
AU - Lores, Pablo
AU - Costa, Monique
AU - Landeira, Mercedes
AU - Rabinovich, Gabriel A.
AU - van Vliet, Sandra J.
AU - Freire, Teresa
N1 - Funding Information: This research was funded by Agencia Nacional de Investigación e Innovación (FCE1-2017-1-136094, ANII, Uruguay) and Comisión Sectorial de Investigación Científica (CSIC, UdelaR, ID114), CSIC Iniciación and, CSIC Grupos-908 I+D (UdelaR) and PEDECIBA. V.d.C. was supported by ANII and by CAP (UdelaR). Publisher Copyright: © 2022 by the authors.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Lung cancer is the first leading cause of cancer-related deaths in the world. Aberrant glycosylation in lung tumors leads to the expression of tumor-associated carbohydrate structures, such as the Tn antigen, consisting of N-acetyl-galactosamine (GalNAc) linked to a serine or threonine residue in proteins (α-GalNAc-O-Ser/Thr). The Tn antigen can be recognized by the Macrophage Galactose/GalNAc lectin (MGL), which mediates various immune regulatory and tolerogenic functions, mainly by reprogramming the maturation of function of dendritic cells (DCs). In this work, we generated two different Tn-expressing variants from the Lewis-type lung murine cancer cell line LL/2, which showed different alterations in the O-glycosylation pathways that influenced the interaction with mouse MGL2 and the immunomodulatory properties of DCs. Thus, the identification of the biological programs triggered by Tn+ cancer cells might contribute to an improved understanding of the molecular mechanisms elicited by MGL-dependent immune regulatory circuits.
AB - Lung cancer is the first leading cause of cancer-related deaths in the world. Aberrant glycosylation in lung tumors leads to the expression of tumor-associated carbohydrate structures, such as the Tn antigen, consisting of N-acetyl-galactosamine (GalNAc) linked to a serine or threonine residue in proteins (α-GalNAc-O-Ser/Thr). The Tn antigen can be recognized by the Macrophage Galactose/GalNAc lectin (MGL), which mediates various immune regulatory and tolerogenic functions, mainly by reprogramming the maturation of function of dendritic cells (DCs). In this work, we generated two different Tn-expressing variants from the Lewis-type lung murine cancer cell line LL/2, which showed different alterations in the O-glycosylation pathways that influenced the interaction with mouse MGL2 and the immunomodulatory properties of DCs. Thus, the identification of the biological programs triggered by Tn+ cancer cells might contribute to an improved understanding of the molecular mechanisms elicited by MGL-dependent immune regulatory circuits.
KW - Macrophage Galactose-type lectin
KW - O-glycosylation
KW - Tn antigen
KW - dendritic cells
KW - lung cancer
UR - http://www.scopus.com/inward/record.url?scp=85139925176&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms231912047
DO - https://doi.org/10.3390/ijms231912047
M3 - Article
C2 - 36233358
SN - 1661-6596
VL - 23
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 19
M1 - 12047
ER -