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Kinin-B1 Receptor Stimulation Promotes Invasion and is Involved in Cell-Cell Interaction of Co-Cultured Glioblastoma and Mesenchymal Stem Cells.
Sci Rep 2018; 8(1):1299SR

Abstract

Glioblastoma multiforme (GBM) represents the most lethal brain tumour, and these tumours have very limited treatment options. Mesenchymal stem cells (MSC) are considered as candidates for advanced cell therapies, due to their tropism towards GBM, possibly affecting their malignancy, thus also representing a potential therapeutic vector. Therefore, we aimed to compare the effects of bone-marrow-derived versus adipose-tissue-derived MSC (BM-/AT-MSC) on heterogeneous populations of tumour cells. This cells' interplay was addressed by the in-vitro two-dimensional (monolayer) and three-dimensional (spheroid) co-culture models, using U87 and U373 GBM cell lines, expressing genotypically different mesenchymal transcriptome profiles. U87 cell low mesenchymal profile expressed high levels of kinin receptor 1 (B1R) and their invasion was greatly enhanced by the B1R agonist des-Arg9-bradykinin upon BM-MSC co-culturing in 3D co-cultures. This correlated to significantly higher cell-cell interactions in U87/BM-MSC mixed spheroids. This was not observed with the U373 cells and not in AT-MSC co-cultures. Altogether, these data support the on-going exploration of B1R as target for adjuvant approach in GBM therapy. Secondly, the results emphasize the need for further careful exploration of the selectivity regarding the origin of MSC as potential candidates for cell therapies, particular in cancer, where they may adversely affect heterogeneous tumour cell populations.

Authors+Show Affiliations

Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineus Prestes 748, São Paulo, SP, 05508-000, Brazil. Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000, Ljubljana, Slovenia. Jožef Stefan International Postgraduate School, Jamova 39, 1000, Ljubljana, Slovenia.Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineus Prestes 748, São Paulo, SP, 05508-000, Brazil.Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000, Ljubljana, Slovenia.Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineus Prestes 748, São Paulo, SP, 05508-000, Brazil. henning@iq.usp.br. Jožef Stefan International Postgraduate School, Jamova 39, 1000, Ljubljana, Slovenia. henning@iq.usp.br.Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000, Ljubljana, Slovenia. Tamara.Lah@nib.si. Jožef Stefan International Postgraduate School, Jamova 39, 1000, Ljubljana, Slovenia. Tamara.Lah@nib.si. Department of Biochemistry, Faculty of Chemistry and Chemical Engineering, University of Ljubljana, Večna pot 113, 1000, Ljubljana, Slovenia. Tamara.Lah@nib.si.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29358738

Citation

Oliveira, Mona N., et al. "Kinin-B1 Receptor Stimulation Promotes Invasion and Is Involved in Cell-Cell Interaction of Co-Cultured Glioblastoma and Mesenchymal Stem Cells." Scientific Reports, vol. 8, no. 1, 2018, p. 1299.
Oliveira MN, Pillat MM, Motaln H, et al. Kinin-B1 Receptor Stimulation Promotes Invasion and is Involved in Cell-Cell Interaction of Co-Cultured Glioblastoma and Mesenchymal Stem Cells. Sci Rep. 2018;8(1):1299.
Oliveira, M. N., Pillat, M. M., Motaln, H., Ulrich, H., & Lah, T. T. (2018). Kinin-B1 Receptor Stimulation Promotes Invasion and is Involved in Cell-Cell Interaction of Co-Cultured Glioblastoma and Mesenchymal Stem Cells. Scientific Reports, 8(1), p. 1299. doi:10.1038/s41598-018-19359-1.
Oliveira MN, et al. Kinin-B1 Receptor Stimulation Promotes Invasion and Is Involved in Cell-Cell Interaction of Co-Cultured Glioblastoma and Mesenchymal Stem Cells. Sci Rep. 2018 01 22;8(1):1299. PubMed PMID: 29358738.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kinin-B1 Receptor Stimulation Promotes Invasion and is Involved in Cell-Cell Interaction of Co-Cultured Glioblastoma and Mesenchymal Stem Cells. AU - Oliveira,Mona N, AU - Pillat,Micheli M, AU - Motaln,Helena, AU - Ulrich,Henning, AU - Lah,Tamara T, Y1 - 2018/01/22/ PY - 2017/07/04/received PY - 2017/12/29/accepted PY - 2018/1/24/entrez PY - 2018/1/24/pubmed PY - 2018/11/24/medline SP - 1299 EP - 1299 JF - Scientific reports JO - Sci Rep VL - 8 IS - 1 N2 - Glioblastoma multiforme (GBM) represents the most lethal brain tumour, and these tumours have very limited treatment options. Mesenchymal stem cells (MSC) are considered as candidates for advanced cell therapies, due to their tropism towards GBM, possibly affecting their malignancy, thus also representing a potential therapeutic vector. Therefore, we aimed to compare the effects of bone-marrow-derived versus adipose-tissue-derived MSC (BM-/AT-MSC) on heterogeneous populations of tumour cells. This cells' interplay was addressed by the in-vitro two-dimensional (monolayer) and three-dimensional (spheroid) co-culture models, using U87 and U373 GBM cell lines, expressing genotypically different mesenchymal transcriptome profiles. U87 cell low mesenchymal profile expressed high levels of kinin receptor 1 (B1R) and their invasion was greatly enhanced by the B1R agonist des-Arg9-bradykinin upon BM-MSC co-culturing in 3D co-cultures. This correlated to significantly higher cell-cell interactions in U87/BM-MSC mixed spheroids. This was not observed with the U373 cells and not in AT-MSC co-cultures. Altogether, these data support the on-going exploration of B1R as target for adjuvant approach in GBM therapy. Secondly, the results emphasize the need for further careful exploration of the selectivity regarding the origin of MSC as potential candidates for cell therapies, particular in cancer, where they may adversely affect heterogeneous tumour cell populations. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/29358738/Kinin_B1_Receptor_Stimulation_Promotes_Invasion_and_is_Involved_in_Cell_Cell_Interaction_of_Co_Cultured_Glioblastoma_and_Mesenchymal_Stem_Cells_ L2 - http://dx.doi.org/10.1038/s41598-018-19359-1 DB - PRIME DP - Unbound Medicine ER -