PubMed Health⌕ Search

Biomedical subjects

Kimmo Porkka

Publications and source records attributed to Kimmo Porkka.

10 recordsLinked to original sources
PubMed2007

Expression of vascular endothelial growth factor receptor 3 and Tie1 tyrosine kinase receptor on acute leukemia cells.

BACKGROUND: Recent data indicate a role for angiogenesis in hematologic malignancies. In addition to promoting new vessel growth in the bone marrow microenvironment, angiogenic factors are regulators of both hematopoietic and leukemic cells. Activation of vascular endothelial growth factor receptor 3 (VEGFR-3) and Tie1 tyrosine kinase receptor are known to promote leukemia cell survival. The details of this complex angiogenesis-related interaction are still uncertain. PROCEDURE: We studied bone marrow samples from 73 patients with acute lymphoblastic (ALL) or myelogenous (AML) leukemia by using immunological methods. RESULTS: Vascular endothelial growth factor receptor 3 expression was found in 15% of the samples, particularly in samples with pediatric lymphoblastic leukemias and monocytic AMLs. Tie1 protein expression was found in 11% of the samples, all of which were from adult AML patients. CONCLUSIONS: Our findings suggest that there are angiogenesis-related differences between pediatric and adult lymphoblastic leukemias as well as between lymphoid and myeloid leukemias.

AC133 Antigen↗
PubMed2003

Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels.

A tumor-homing peptide, F3, selectively binds to endothelial cells in tumor blood vessels and to tumor cells. Here, we show that the cell surface molecule recognized by F3 is nucleolin. Nucleolin specifically bound to an F3 peptide affinity matrix from extracts of cultured breast carcinoma cells. Antibodies and cell surface biotin labeling revealed nucleolin at the surface of actively growing cells, and these cells bound and internalized fluorescein-conjugated F3 peptide, transporting it into the nucleus. In contrast, nucleolin was exclusively nuclear in serum-starved cells, and F3 did not bind to these cells. The binding and subsequent internalization of F3 were blocked by an antinucleolin antibody. Like the F3 peptide, intravenously injected antinucleolin antibodies selectively accumulated in tumor vessels and in angiogenic vessels of implanted "matrigel" plugs. These results show that cell surface nucleolin is a specific marker of angiogenic endothelial cells within the vasculature. It may be a useful target molecule for diagnostic tests and drug delivery applications.

Active Transport, Cell Nucleus↗
PubMed2003

Progressive vascular changes in a transgenic mouse model of squamous cell carcinoma.

Phage display was used to identify homing peptides for blood vessels in a mouse model of HPV16-induced epidermal carcinogenesis. One peptide, CSRPRRSEC, recognized the neovasculature in dysplastic skin but not in carcinomas. Two other peptides, with the sequences CGKRK and CDTRL, preferentially homed to neovasculature in tumors and, to a lesser extent, premalignant dysplasias. The peptides did not home to vessels in normal skin, other normal organs, or the stages in pancreatic islet carcinogenesis in another mouse model. The CGKRK peptide may recognize heparan sulfates in tumor vessels. The dysplasia-homing peptide is identical to a loop in kallikrein-9 and may bind a kallikrein inhibitor or substrate. Thus, characteristics of the angiogenic vasculature distinguish premalignant and malignant stages of skin tumorigenesis.

Animals↗
PubMed2002

A tumor-homing peptide with a targeting specificity related to lymphatic vessels.

Blood vessels of tumors carry specific markers that are usually angiogenesis-related. We previously used phage-displayed peptide libraries in vivo to identify peptides that home to tumors through the circulation and that specifically bind to the endothelia of tumor blood vessels. Here we devised a phage screening procedure that would favor tumor-homing to targets that are accessible to circulating phage, but are not blood vessels. Screening on MDA-MB-435 breast carcinoma xenografts yielded multiple copies of a phage that displays a cyclic 9-amino-acid peptide, LyP-1. Homing and binding to tumor-derived cell suspensions indicated that LyP-1 also recognizes an osteosarcoma xenograft, and spontaneous prostate and breast cancers in transgenic mice, but not two other tumor xenografts. Fluorescein-labeled LyP-1 peptide was detected in tumor structures that were positive for three lymphatic endothelial markers and negative for three blood vessel markers. LyP-1 accumulated in the nuclei of the putative lymphatic cells, and in the nuclei of tumor cells. These results suggest that tumor lymphatics carry specific markers and that it may be possible to specifically target therapies into tumor lymphatics.

Animals↗
PubMed2002

A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo.

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.

Animals↗