The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo
Open accessAbstract
We used a screening procedure to identify protein domains from phage-displayed cDNA libraries that bind both to bone marrow endothelial progenitor cells and tumor vasculature. Screening phage for binding of progenitor cell-enriched bone marrow cells in vitro , and for homing to HL-60 human leukemia cell xenograft tumors in vivo , yielded a cDNA fragment that encodes an N-terminal fragment of human high mobility group protein 2 (HMGN2, formerly HMG-17). Upon i.v. injection, phage displaying this HMGN2 fragment homed to HL-60 and MDA-MB-435 tumors. Testing of subfragments localized the full binding activity to a 31-aa peptide (F3) in the HMGN2 sequence. Fluorescein-labeled F3 peptide bound to and was internalized by HL-60 cells and human MDA-MB-435 breast cancer cells, appearing initially in the cytoplasm and then in the nuclei of these cells. Fluorescent F3 accumulated in HL-60 and MDA-MB-435 tumors after an i.v. injection, appearing in the nuclei of tumor endothelial cells and tumor cells. Thus, F3 can carry a payload (phage, fluorescein) to a tumor and into the cell nuclei in the tumor. This peptide may be suitable for targeting cytotoxic drugs and gene therapy vectors into tumors.
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Cites
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Cited by
Åkerman, M. E., Chan, W. C. W., Laakkonen, P., Bhatia, S. N., & Ruoslahti, E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152463399 · Cited by 1,437
Self-citationCoadministration of a Tumor-Penetrating Peptide Enhances the Efficacy of Cancer Drugs
Sugahara, K. N., Teesalu, T., Karmali, P. P., Kotamraju, V. R., Agemy, L., Greenwald, D. R., & Ruoslahti, E. (2010) · Science · doi:10.1126/science.1183057 · Cited by 1,075
Self-citationC-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration
Teesalu, T., Sugahara, K. N., Kotamraju, V. R., & Ruoslahti, E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908201106 · Cited by 812
Self-citationA tumor-homing peptide with a targeting specificity related to lymphatic vessels
Laakkonen, P., Porkka, K., Hoffman, J. A., & Ruoslahti, E. (2002) · Nature Medicine · doi:10.1038/nm720 · Cited by 498
Self-citationTumor penetrating peptides for improved drug delivery
Ruoslahti, E. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.03.008 · Cited by 459
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Metadata
- Authors
- Porkka, K., Laakkonen, P., Hoffman, J. A., Bernasconi, M., & Ruoslahti, E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-05-21
- Volume
- 99
- Issue
- 11
- Pages
- 7444-7449
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2142536456
- Cited by
- 291
- References
- 6
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- green
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