Author(s): Porkka K, Laakkonen P, Hoffman JA, Bernasconi M, Ruoslahti E, Porkka K, Laakkonen P, Hoffman JA, Bernasconi M, Ruoslahti E, Porkka K, Laakkonen P, Hoffman JA, Bernasconi M, Ruoslahti E, Porkka K, Laakkonen P, Hoffman JA, Bernasconi M, Ruoslahti E
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Abstract 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.
This article was published in Proc Natl Acad Sci U S A
and referenced in Research & Reviews: Journal of Botanical Sciences