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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Kinin-B1 Receptor Stimulation Promotes Invasion and is Involved in Cell-Cell Interaction of Co-Cultured Glioblastoma and Mesenchymal Stem Cells

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Author(s):
Oliveira, Mona N. [1, 2, 3] ; Pillat, Micheli M. [1] ; Motaln, Helena [3] ; Ulrich, Henning [1, 2] ; Lah, Tamara T. [2, 3, 4]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Av Prof Lineus Prestes 748, BR-05508000 Sao Paulo, SP - Brazil
[2] Jozef Stefan Int, Postgrad Sch, Jamova 39, Ljubljana 1000 - Slovenia
[3] Natl Inst Biol, Dept Genet Toxicol & Canc Biol, Vecna Pot 111, Ljubljana 1000 - Slovenia
[4] Univ Ljubljana, Fac Chem & Chem Engn, Dept Biochem, Vecna Pot 113, Ljubljana 1000 - Slovenia
Total Affiliations: 4
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 8, JAN 22 2018.
Web of Science Citations: 4
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-Arg(9)-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. (AU)

FAPESP's process: 12/50880-4 - Stem cells: from basic studies of kinin and purinergic receptor roles towards therapeutical applications
Grantee:Alexander Henning Ulrich
Support Opportunities: Research Projects - Thematic Grants