Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival.

Cancers (Basel) 2019 Apr 25;11(4). Epub 2019 Apr 25.

Xintela AB, Medicon Village, SE-223 81 Lund, Sweden.

New, effective treatment strategies for glioblastomas (GBMs), the most malignant and invasive brain tumors in adults, are highly needed. In this study, we investigated the potential of integrin α10β1 as a therapeutic target in GBMs. Expression levels and the role of integrin α10β1 were studied in patient-derived GBM tissues and cell lines. The effect of an antibody-drug conjugate (ADC), an integrin α10 antibody conjugated to saporin, on GBM cells and in a xenograft mouse model was studied. We found that integrin α10β1 was strongly expressed in both GBM tissues and cells, whereas morphologically unaffected brain tissues showed only minor expression. Partial or no overlap was seen with integrins α3, α6, and α7, known to be expressed in GBM. Further analysis of a subpopulation of GBM cells selected for high integrin α10 expression demonstrated increased proliferation and sphere formation. Additionally, siRNA-mediated knockdown of integrin α10 in GBM cells led to decreased migration and increased cell death. Furthermore, the ADC reduced viability and sphere formation of GBM cells and induced cell death both and . Our results demonstrate that integrin α10β1 has a functional role in GBM cells and is a novel, potential therapeutic target for the treatment of GBM.

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11040587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521287PMC
April 2019

Publication Analysis

Top Keywords

gbm cells
20
integrin α10β1
16
integrin α10
16
therapeutic target
12
gbm
9
cell death
8
sphere formation
8
integrin
8
expressed gbm
8
gbm tissues
8
cells
6
partial overlap
4
expression partial
4
conjugate adc
4
tissues minor
4
adc integrin
4
overlap integrins
4
minor expression
4
α3 α6
4
gbm analysis
4

References

(Supplied by CrossRef)

Similar Publications