Dual Targeting of Stromal Cell Support and Leukemic Cell Growth by a Peptidic PKC Inhibitor Shows Effectiveness against B-ALL

Autor: Jean-Paul Vernot, Jessica Flechas-Afanador, Camila Cadavid-Cortés, Natalia-Del Pilar Vanegas, Gloria Inés Uribe, Jimmy Lagos, Paola Ortiz-Montero, Adriana Linares-Ballesteros, Paola Fernanda Ruiz-Aparicio
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Integrins
lcsh:Chemistry
Jurkat Cells
0302 clinical medicine
PKC
Enzyme Inhibitors
Child
lcsh:QH301-705.5
Spectroscopy
Cells
Cultured
Protein Kinase C
B-Lymphocytes
Chemistry
Cell adhesion molecule
B-ALL
General Medicine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Intercellular Adhesion Molecule-1
Recombinant Proteins
Computer Science Applications
030220 oncology & carcinogenesis
Oligopeptides
Intracellular
Stromal cell
Antineoplastic Agents
chimeric peptide
Catalysis
Article
Inorganic Chemistry
mesenchymal support
03 medical and health sciences
Humans
Physical and Theoretical Chemistry
Cell adhesion
Molecular Biology
Protein kinase C
Cell Proliferation
Cell growth
Organic Chemistry
Mesenchymal stem cell
cell adhesion
Mesenchymal Stem Cells
leukemic microenvironment
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Cell culture
Cancer research
K562 Cells
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 21, Iss 3705, p 3705 (2020)
Volume 21
Issue 10
ISSN: 1422-0067
Popis: Mesenchymal stem cells (MSC) favour a scenario where leukemic cells survive. The protein kinase C (PKC) is essential to confer MSC support to leukemic cells and may be responsible for the intrinsic leukemic cell growth. Here we have evaluated the capacity of a chimeric peptide (HKPS), directed against classical PKC isoforms, to inhibit leukemic cell growth. HKPS was able to strongly inhibit viability of different leukemic cell lines, while control HK and PS peptides had no effect. Further testing showed that 30% of primary samples from paediatric B-cell acute lymphoblastic leukaemia (B-ALL) were also strongly affected by HKPS. We showed that HKPS disrupted the supportive effect of MSC that promote leukemic cell survival. Interestingly, ICAM-1 and VLA-5 expression increased in MSC during the co-cultures with B-ALL cells, and we found that HKPS inhibited the interaction between MSC and B-ALL cells due to a reduction in the expression of these adhesion molecules. Of note, the susceptibility of B-ALL cells to dexamethasone increased when MSC were treated with HKPS. These results show the relevance of these molecular interactions in the leukemic niche. The use of HKPS may be a new strategy to disrupt intercellular communications, increasing susceptibility to therapy, and at the same time, directly affecting the growth of PKC-dependent leukemic cells.
Databáze: OpenAIRE
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