Isolation and Properties of Tumor‐derived Endothelial Cells from Rat KMT‐17 Fibrosarcoma

Utoguchi, Naoki; Dantakean, A; Makimoto, Hiroo; Wakai, Yukiko; Tsutsumi, Yasuo; Nakagawa, Shinsaku; Mayumi, Tadanori

doi:10.1111/j.1349-7006.1995.tb03039.x

Cited by 14 publications

(18 citation statements)

References 40 publications

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“…First, the permeability of tumor blood vessels and tumor vasculature is higher than that of normal blood vessels, both in vitro and in vivo. [14][15][16] Second, less interaction between blood vessels and leukocytes is observed in tumor compared to normal microvessels. 14,17,18) In previous studies, we have shown that tumor-derived endothelial cells (TEC), isolated from a rat KMT-17 fibrosarcoma, pas- 3 To whom correspondence should be addressed.…”

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confidence: 99%

Preferential Activity of Wild‐type and Mutant Tumor Necrosis Factor‐α against Tumor‐derived Endothelial‐like Cells

Kuroda

Miyata

Tsutsumi

et al. 2000

Japanese Journal of Cancer Research

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Tumor-derived endothelial-like cells (tEC) were prepared by culturing human umbilical vein endothelial cells (HUVEC) in the presence of HT1080 human fibrosarcoma-conditioned medium. tEC showed higher permeability and less cell-adhesion activity than normal HUVEC (nEC). Tumor necrosis factor-α α α α (TNF) is known to have tumor-vasculature disrupting activity. tEC showed higher cytotoxicity to recombinant human TNF (rhTNF) than nEC, and was not observed using HUVEC cultured with WI38 human diploid cell-conditioned medium as a medium-control. These results demonstrate that tEC acquire physiological properties of tumor-associated vasculature, and may be a useful model system for the study of the mechanisms of TNF antitumor action. The TNF-mutant RGD-V29 (code No. F4614), which has an inserted 4 Arg-Gly-Asp sequence and an 29 Arg→ → → →Val replacement, was found to induce greater preferential destruction of tEC compared to rhTNF. When the preferential activities were evaluated in terms of 30% cytotoxicity (IC 30 ) ratio (nEC/tEC), the ratio was 460 for RGD-V29 compared to 4.2 for rhTNF. RGD-V29 also exhibited cell-adhesive function and bound preferentially to the p55 TNF-receptor. Both these properties of RGD-V29 contributed to the tEC selective cytotoxicity, indicating that the RGD ligands and selective p55 receptor binding on the cells, although uncharacterized, are involved in tEC targeting. Therefore, the TNF mutant RGD-V29 may show greater selectivity toward tumor vasculature than wild-type TNF.

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confidence: 99%

Preferential Activity of Wild‐type and Mutant Tumor Necrosis Factor‐α against Tumor‐derived Endothelial‐like Cells

Kuroda

Miyata

Tsutsumi

et al. 2000

Japanese Journal of Cancer Research

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“…Monoclonal antibodies TES-23 (tumor endothelium-specific mouse monoclonal antibody) was prepared as described previously. 14,15) Mopc was prepared from the mouse plasmacytoma MOPC-31C (ATCC. CCL-130) as a nonspecific control antibody.…”

Section: Methodsmentioning

confidence: 99%

“…To prepare such antibodies, we previously isolated and cultivated endothelial cells (TEC) from KMT-17 fibrosarcoma, and examined their properties in culture. 14) We then prepared the monoclonal antibody TES-23 against tumor tissue endothelial cells by immunization of mice with TEC. 15) Next, we immunoconjugated TES-23 with neocarzinostatin (NCS).…”

mentioning

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Effective Cancer Targeting Using an Anti‐tumor Tissue Vascular Endotheliumspecific Monoclonal Antibody (TES‐23)

Wakai

Matsui

Koizumi

et al. 2000

Japanese Journal of Cancer Research

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“…TECs, or capillary endothelial cells in tumour tissue, were isolated from KMT-17 rat fibrosarcoma (kindly donated by Dr N Takeichi, Hokkaido University, Japan) by means of density-gradient centrifugation and attach-speed separation techniques as we previously reported (Utoguchi et al, 1995a). Briefly, minced and collagenasedigested KMT-17 tumour tissue was separated by Percoll (Amersham Pharmacia Biotech, Sweden) density-gradient centrifugation.…”

Section: Isolation Of Tumour Endothelial Cellsmentioning

confidence: 99%

“…Up to now only a few studies have been reported concerning the isolation and culture of tumour vascular endothelium, so the search for molecules expressed specifically on tumour vascular endothelium was extremely difficult. We recently established a method for isolating tumour vascular endothelial cells (TECs) from KMT-17 rat fibrosarcoma (Utoguchi et al, 1995a). TECs will make it possible to discover new antigens specific to tumour vascular endothelium.…”

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confidence: 99%

Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: A novel drug carrier for cancer targeting therapy

et al. 1999

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SummaryThe tissue distribution of anti-tumour vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles from isolated rat tumour-derived endothelial cells (TECs) was assessed in various tumour-bearing animals. Radiolabelled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, the source of isolated TECs after intravenous injection. In Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumour tissue in nude mice, radioactivities of 125 I-labelled TES-23 were also up to 50 times higher than those of control antibody with little distribution to normal tissues. The selective recognition of TES-23 to TECs was competitively blocked by preadministration of unlabelled TES-23 in vivo. Furthermore, immunostaining of human tissue sections showed specific binding of TES-23 on endothelium in oesophagus cancers. These results indicate that tumour vascular endothelial cells express common antigen in different tumour types of various animal species. In order to clarify the efficacy of TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neocarzinostatin, was tested for its anti-tumour effect in rats bearing KMT-17 fibrosarcomas. The immunoconjugate (TES-23-NCS) caused marked regression of the tumour, accompanied by haemorrhagic necrosis. Thus, from a clinical view, TES-23 would be a novel drug carrier because of its high specificity to tumour vascular endothelium and its application to many types of cancer. © 1999 Cancer Research Campaign Keywords: tumour vascular endothelium; immunoconjugate; targeting therapy; drug delivery system; monoclonal antibody 1155British Journal of Cancer (1999) 81(7), 1155-1161 © 1999 Cancer Research Campaign Article no. bjoc.1999 Received 30 June 1998 Revised 2 December 1998 Accepted 12 May 1999 Correspondence to: T Mayumi antibody (TES-23) that recognizes TECs by means of actively immunizing mice with membranes of TECs after passive immunization with endothelial cells derived from normal tissue (Ohizumi et al, 1997). This study was conducted to assess the distribution of the antigen recognized by TES-23 in many tumour types in mice, rats and humans, and suggests the usefulness of TES-23 for a targeting therapy against tumour vasculature. MATERIALS AND METHODS Isolation of tumour endothelial cellsTECs, or capillary endothelial cells in tumour tissue, were isolated from KMT-17 rat fibrosarcoma (kindly donated by Dr N Takeichi, Hokkaido University, Japan) by means of density-gradient centrifugation and attach-speed separation techniques as we previously reported (Utoguchi et al, 1995a). Briefly, minced and collagenasedigested KMT-17 tumour tissue was separated by Percoll (Amersham Pharmacia Biotech, Sweden) density-gradient centrifugation. The cells in the fraction enriched with endothelial cells were plated on tissue culture dishes in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal calf serum (FCS) and 50 µg ml -1 of endothelial cell growth supplement (ECGS, Sigma Chemical Co., St Lo...

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Isolation and Properties of Tumor‐derived Endothelial Cells from Rat KMT‐17 Fibrosarcoma

Cited by 14 publications

References 40 publications

Preferential Activity of Wild‐type and Mutant Tumor Necrosis Factor‐α against Tumor‐derived Endothelial‐like Cells

Preferential Activity of Wild‐type and Mutant Tumor Necrosis Factor‐α against Tumor‐derived Endothelial‐like Cells

Effective Cancer Targeting Using an Anti‐tumor Tissue Vascular Endotheliumspecific Monoclonal Antibody (TES‐23)

Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: A novel drug carrier for cancer targeting therapy

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