Tumor-penetrating therapy for β5 integrin-rich pancreas cancer

Tatiana Hurtado de Mendoza, Evangeline S. Mose, Gregory P. Botta, Gary B. Braun, Venkata R. Kotamraju, Randall P. French, Kodai Suzuki, Norio Miyamura, Tambet Teesalu, Erkki Ruoslahti, Andrew M. Lowy () and Kazuki N. Sugahara ()
Additional contact information
Tatiana Hurtado de Mendoza: Sanford-Burnham-Prebys Medical Discovery Institute
Evangeline S. Mose: University of California
Gregory P. Botta: Sanford-Burnham-Prebys Medical Discovery Institute
Gary B. Braun: Sanford-Burnham-Prebys Medical Discovery Institute
Venkata R. Kotamraju: Sanford-Burnham-Prebys Medical Discovery Institute
Randall P. French: University of California
Kodai Suzuki: Columbia University Vagelos College of Physicians and Surgeons
Norio Miyamura: Columbia University Vagelos College of Physicians and Surgeons
Tambet Teesalu: Sanford-Burnham-Prebys Medical Discovery Institute
Erkki Ruoslahti: Sanford-Burnham-Prebys Medical Discovery Institute
Andrew M. Lowy: University of California
Kazuki N. Sugahara: Sanford-Burnham-Prebys Medical Discovery Institute

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by marked desmoplasia and drug resistance due, in part, to poor drug delivery to extravascular tumor tissue. Here, we report that carcinoma-associated fibroblasts (CAFs) induce β5 integrin expression in tumor cells in a TGF-β dependent manner, making them an efficient drug delivery target for the tumor-penetrating peptide iRGD. The capacity of iRGD to deliver conjugated and co-injected payloads is markedly suppressed when β5 integrins are knocked out in the tumor cells. Of note, β5 integrin knock-out in tumor cells leads to reduced disease burden and prolonged survival of the mice, demonstrating its contribution to PDAC progression. iRGD significantly potentiates co-injected chemotherapy in KPC mice with high β5 integrin expression and may be a powerful strategy to target an aggressive PDAC subpopulation.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-21858-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21858-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-21858-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().