Kinins in Glioblastoma Microenvironment

  • Mona N. Oliveira
  • Barbara BreznikEmail author
  • Micheli M. Pillat
  • Ricardo L. Pereira
  • Henning Ulrich
  • Tamara T. Lah
Original Article


Tumour progression involves interactions among various cancer cell clones, including the cancer stem cell subpopulation and exogenous cellular components, termed cancer stromal cells. The latter include a plethora of tumour infiltrating immunocompetent cells, among which are also immuno-modulatory mesenchymal stem cells, which by vigorous migration to growing tumours and susequent transdifferentiation into various types of tumour-residing stromal cells, may either inhibit or support tumour progression. In the light of the scarce therapeutic options existing for the most malignant brain tumour glioblastoma, mesenchymal stem cells may represent a promising novel tool for cell therapy, e.g. drug delivery vectors. Here, we review the increasing number of reports on mutual interactions between mesenchymal stem cells and glioblastoma cells in their microenvironment. We particularly point out two novel aspects: the different responses of cancer cells to their microenvironmental cues, and to the signalling by kinin receptors that complement the immuno-modulating cytokine-signalling networks. Inflammatory glioblastoma microenvironment is characterised by increasing expression of kinin receptors during progressive glioma malignancy, thus making kinin signalling and kinins themselves rather important in this context. In general, their role in tumour microenvironment has not been explored so far. In addition, kinins also regulate blood brain barrier-related drug transfer as well as brain tumour angiogenesis. These studies support the on-going research on kinin antagonists as candidates in the development of anti-invasive agents for adjuvant glioblastoma therapy.


Co-culture Glioma Kinin receptors Mesenchymal stem cells Microenvironment Tumour heterogeneity 



We acknowledge the support by an ARRS Programme P1-0245 awarded to TTL in Slovenia and the National Counsel of Technological and Scientific Development granted to HU with a Visiting Professorship (CNPq Linha 2 – Bolsa Pesquisador Visitante Especial, Edital No 61/2011) awarded to TTL in Brazil. HU further acknowledges grant support from the São Paulo Research Foundation (FAPESP proj. No. 2012/50880-4). BB was a PhD Fellow of the Jožef Stefan International Postgraduate School, Ljubljana, Slovenia. MNO was a double PhD fellow at the Biochemistry Department of the University of São Paulo-Brazil and Fellow of the Jožef Stefan International Postgraduate School, Ljubljana, Slovenia, with a fellowship from National Counsel of Technological and Scientific Development (CNPq). RLP is a graduate student at the Biochemistry Department of the University of São Paulo, with a fellowship for his PhD thesis granted by the Coordination for the Improvement of Higher Education Personnel (CAPES), Brazil. We thank Dr. Miloš Vittori for images of glioblastoma tumours in zebrafish embryos.

Author Contributions

BB and MNO share first authorship, TTL and HU share correspondence.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Biochemistry, Institute of ChemistryUniversity of São PauloSão PauloBrazil
  2. 2.Jožef Stefan International Postgraduate SchoolLjubljanaSlovenia
  3. 3.Department of Genetic Toxicology and Cancer BiologyNational Institute of BiologyLjubljanaSlovenia
  4. 4.Department of Biochemistry, Faculty of Chemistry and Chemical EngineeringUniversity of LjubljanaLjubljanaSlovenia

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