Abstract
All cells expel a variety of nanosized extracellular vesicles (EVs), including exosomes, with composition reflecting the cells' biological state. Cancer pathology is dramatically mediated by EV trafficking via key proteins, lipids, metabolites, and microRNAs. Recent proteomics evidence suggests that tumor-associated exosomes exhibit distinct expression of certain membrane proteins, rendering those proteins as attractive targets for diagnostic or therapeutic application, yet it is not currently feasible to distinguish circulating EVs in complex biofluids according to their tissue of origin or state of disease. Here, peptide binding to tumor-associated EVs via overexpressed membrane protein is demonstrated. It is found that SKOV-3 ovarian tumor cells and their released EVs express α 3 β 1 integrin, which can be targeted by the in-house cyclic nonapeptide, LXY30. After measuring bulk SKOV-3 EV association with LXY30 by flow cytometry, Raman spectral analysis of laser-trapped single exosomes with LXY30-dialkyne conjugate enables the differentiation of cancer-associated exosomes from noncancer exosomes. Furthermore, the foundation for a highly specific detection platform for tumor-EVs in solution with biosensor surface-immobilized LXY30 is introduced. LXY30 not only exhibits high specificity and affinity to α 3 β 1 integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.
| Original language | English (US) |
|---|---|
| Article number | 1600038 |
| Journal | Advanced Biosystems |
| Volume | 1 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2017 |
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Keywords
- biosensors
- cancer
- diagnostics
- exosomes
- optical tweezers
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biomaterials
- Biomedical Engineering
Cite this
Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides. / Carney, Randy; Hazari, Sidhartha; Rojalin, Tatu; Knudson, Alisha; Gao, Tingjuan; Tang, Yuchen; Liu, Ruiwu; Viitala, Tapani; Yliperttula, Marjo; Lam, Kit.
In: Advanced Biosystems, Vol. 1, No. 5, 1600038, 01.05.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides
AU - Carney, Randy
AU - Hazari, Sidhartha
AU - Rojalin, Tatu
AU - Knudson, Alisha
AU - Gao, Tingjuan
AU - Tang, Yuchen
AU - Liu, Ruiwu
AU - Viitala, Tapani
AU - Yliperttula, Marjo
AU - Lam, Kit
PY - 2017/5/1
Y1 - 2017/5/1
N2 - All cells expel a variety of nanosized extracellular vesicles (EVs), including exosomes, with composition reflecting the cells' biological state. Cancer pathology is dramatically mediated by EV trafficking via key proteins, lipids, metabolites, and microRNAs. Recent proteomics evidence suggests that tumor-associated exosomes exhibit distinct expression of certain membrane proteins, rendering those proteins as attractive targets for diagnostic or therapeutic application, yet it is not currently feasible to distinguish circulating EVs in complex biofluids according to their tissue of origin or state of disease. Here, peptide binding to tumor-associated EVs via overexpressed membrane protein is demonstrated. It is found that SKOV-3 ovarian tumor cells and their released EVs express α 3 β 1 integrin, which can be targeted by the in-house cyclic nonapeptide, LXY30. After measuring bulk SKOV-3 EV association with LXY30 by flow cytometry, Raman spectral analysis of laser-trapped single exosomes with LXY30-dialkyne conjugate enables the differentiation of cancer-associated exosomes from noncancer exosomes. Furthermore, the foundation for a highly specific detection platform for tumor-EVs in solution with biosensor surface-immobilized LXY30 is introduced. LXY30 not only exhibits high specificity and affinity to α 3 β 1 integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.
AB - All cells expel a variety of nanosized extracellular vesicles (EVs), including exosomes, with composition reflecting the cells' biological state. Cancer pathology is dramatically mediated by EV trafficking via key proteins, lipids, metabolites, and microRNAs. Recent proteomics evidence suggests that tumor-associated exosomes exhibit distinct expression of certain membrane proteins, rendering those proteins as attractive targets for diagnostic or therapeutic application, yet it is not currently feasible to distinguish circulating EVs in complex biofluids according to their tissue of origin or state of disease. Here, peptide binding to tumor-associated EVs via overexpressed membrane protein is demonstrated. It is found that SKOV-3 ovarian tumor cells and their released EVs express α 3 β 1 integrin, which can be targeted by the in-house cyclic nonapeptide, LXY30. After measuring bulk SKOV-3 EV association with LXY30 by flow cytometry, Raman spectral analysis of laser-trapped single exosomes with LXY30-dialkyne conjugate enables the differentiation of cancer-associated exosomes from noncancer exosomes. Furthermore, the foundation for a highly specific detection platform for tumor-EVs in solution with biosensor surface-immobilized LXY30 is introduced. LXY30 not only exhibits high specificity and affinity to α 3 β 1 integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.
KW - biosensors
KW - cancer
KW - diagnostics
KW - exosomes
KW - optical tweezers
UR - http://www.scopus.com/inward/record.url?scp=85054719617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054719617&partnerID=8YFLogxK
U2 - 10.1002/adbi.201600038
DO - 10.1002/adbi.201600038
M3 - Article
AN - SCOPUS:85054719617
VL - 1
JO - Advanced Biosystems
JF - Advanced Biosystems
SN - 2366-7478
IS - 5
M1 - 1600038
ER -