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Exogenous introduct...
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Johansson, ErikGothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine
(author)
Exogenous introduction of tissue inhibitor of metalloproteinase 2 reduces accelerated growth of TGF-β-disrupted diffuse-type gastric carcinoma.
- Article/chapterEnglish2010
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Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/132032
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https://gup.ub.gu.se/publication/132032URI
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https://doi.org/10.1111/j.1349-7006.2010.01688.xDOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Diffuse-type gastric carcinoma is characterized by rapid progression and poor prognosis. High expression of transforming growth factor (TGF)-β and thick stromal fibrosis are observed in this type of gastric carcinoma. We have previously shown that disruption of TGF-β signaling via introduction of a dominant negative form of the TGF-β type II receptor (dnTβRII) into diffuse-type gastric cancer cell lines, including OCUM-2MLN, caused accelerated tumor growth through induction of tumor angiogenesis in vivo. In the present study, we show that TGF-β induces upregulation of expression of tissue inhibitor of metalloproteinase 2 (TIMP2) in the OCUM-2MLN cell line in vitro, and that expression of TIMP2 is repressed by dnTβRII expression in vivo. Transplantation of the OCUM-2MLN cells to nude mice exhibited accelerated tumor growth in response to dnTβRII expression, which was completely abolished when TIMP2 was coexpressed with dnTβRII. Although the blood vessel density of TIMP2-expressing tumors was only slightly decreased, the degree of hypoxia in tumor tissues was significantly increased and pericytes covering tumor vasculature were decreased by TIMP2 expression in OCUM-2MLN cells, suggesting that the function of tumor vasculatures was repressed by TIMP2 and consequently tumor growth was reduced. These findings provide evidence that one of the mechanisms of the increase in angiogenesis in diffuse-type gastric carcinoma is the downregulation of the anti-angiogenic protein TIMP2.
Subject headings and genre
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MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
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MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
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Animals
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Anoxia
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Cell Line
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Tumor
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Cell Proliferation
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drug effects
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Gene Expression Regulation
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Neoplastic
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drug effects
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Humans
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Immunoblotting
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Immunohistochemistry
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Male
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Mice
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Mice
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Inbred BALB C
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Mice
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Nude
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Neoplasms
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Experimental
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genetics
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metabolism
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pathology
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Neovascularization
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Pathologic
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genetics
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metabolism
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pathology
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Protein-Serine-Threonine Kinases
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genetics
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metabolism
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Receptors
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Transforming Growth Factor beta
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genetics
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metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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drug effects
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Stomach Neoplasms
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genetics
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metabolism
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pathology
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Tissue Inhibitor of Metalloproteinase-2
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genetics
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metabolism
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Transforming Growth Factor beta
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metabolism
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pharmacology
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Transplantation
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Heterologous
Added entries (persons, corporate bodies, meetings, titles ...)
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Komuro, Akiyoshi
(author)
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Iwata, Caname
(author)
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Hagiwara, Akifumi
(author)
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Fuse, Yuma
(author)
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Watanabe, Akira
(author)
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Morishita, Yasuyuki
(author)
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Aburatani, Hiroyuki
(author)
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Funa, Keiko,1949Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xfunke
(author)
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Kano, Mitsunobu R
(author)
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Miyazono, Kohei
(author)
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Göteborgs universitetInstitutionen för biomedicin
(creator_code:org_t)
Related titles
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In:Cancer science: Wiley101:11, s. 2398-4031349-70061347-9032
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Johansson, Erik
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Komuro, Akiyoshi
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Iwata, Caname
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Hagiwara, Akifum ...
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Fuse, Yuma
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Watanabe, Akira
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Morishita, Yasuy ...
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Aburatani, Hiroy ...
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Funa, Keiko, 194 ...
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Miyazono, Kohei
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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Cancer science
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University of Gothenburg