Conditioned media of carcinoma cells cultured in hypoxic microenvironment stimulate angiogenesis in vitro; relationship to basic fibroblast growth factor

Ishibashi, Hiroyuki; Nakagawa, Kei; Nakashima, Yutaka; Sueishi, Katsuo

doi:10.1007/bf00199343

Cited by 18 publications

(10 citation statements)

References 44 publications

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“…Compared with other angiogenic cytokines such as VEGF, FGF2 induces endothelial cell proliferation to a greater extent [32]. Many embryonic germ layer-derived cells and endothelial cells themselves secrete FGF2 [33], which may maintain endothelial cell growth via autocrine and paracrine signaling. FGF2 binds heparan sulfate within the extracellular matrix of basement membrane cells and is stored within the tissue.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Induces FGF2 Production by Vascular Endothelial Cells and Alters MMP9 and TIMP1 Expression in Extravillous Trophoblasts and Their Invasiveness in a Cocultured Model

Luo

Qiao

Yin

2011

Journal of Reproduction and Development

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The role of fibroblast growth factor 2 (FGF2) secretion by vascular endothelial cells during trophoblast invasion was assessed. The human extravillous trophoblast cell line, TEV-1, and umbilical vein endothelial cell line, HUVE-12, were cocultured under normal and hypoxic conditions. FGF2 expression in HUVE-12 cells and matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1) expression in TEV-1 cells were analyzed using quantitative RT-PCR and Western blot analyses. TEV-1 cell invasion was also examined. FGF2 expression in the HUVE-12 cells cocultured with TEV-1 cells was significantly increased under hypoxic conditions. In the TEV-1 cells cocultured with HUVE-12, hypoxia reduced MMP9 expression and increased TIMP1 expression; it also reduced cell invasion by 43%. However, the expression of MMP9 and TIMP1 and ratio of MMP9/TIMP1 were increased when the TEV-1 cells were cultured alone under hypoxic conditions. These findings suggest that FGF2 release by stressed endothelial cells of uterine spiral arteries play roles in decreasing MMP9 and increasing TIMP1 production in extravillous trophoblasts (EVT) in response to stress, resulting in reduced EVT invasion and possibly shallow implantation of the placenta.

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Section: Discussionmentioning

confidence: 99%

Hypoxia Induces FGF2 Production by Vascular Endothelial Cells and Alters MMP9 and TIMP1 Expression in Extravillous Trophoblasts and Their Invasiveness in a Cocultured Model

Luo

Qiao

Yin

2011

Journal of Reproduction and Development

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“…For example, hypoxia has been shown to promote collagen synthesis in wounds (2). Likewise, hypoxia potentiates angiogenesis (48,49) and promotes TGF-␤-mediated deposition of collagen (50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia increases human keratinocyte motility on connective tissue.

O’Toole¹,

Marinkovich²,

Peavey³

et al. 1997

J. Clin. Invest.

115

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Re-epithelialization of skin wounds depends upon the migration of keratinocytes from the cut margins of the wound and is enhanced when human keratinocytes are covered with occlusive dressings that induce hypoxia. In this study, two independent migration assays were used to compare cellular motility on connective tissue components under normoxic or hypoxic conditions. Human keratinocytes apposed to collagens or fibronectin exhibited increased motility when subjected to hypoxic (0.2 or 2% oxygen) conditions compared with normoxic (9 or 20% oxygen) conditions. When compared with normoxic cells, hypoxic keratinocytes exhibited increased expression and redistribution of the lamellipodia-associated proteins (ezrin, radixin, and moesin). Furthermore, hypoxic keratinocytes demonstrated decreased secretion of laminin-5, a laminin isoform known to inhibit keratinocyte motility. Hypoxia did not alter the number of integrin receptors on the cell surface, but did induce enhanced secretion of the 92-kD type IV collagenase. These data demonstrate that hypoxia promotes human keratinocyte motility on connective tissue. Hypoxia-driven motility is associated with increased expression of lamellipodia proteins, increased expression of collagenase and decreased expression of laminin-5, the locomotion brake for keratinocytes. (

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“…CMs were prepared by MSC culture and HT1080 cell culture following the procedures described in previous studies . Cells were plated on culture dishes at an over‐confluent density (4 × 10 4 cells/cm 2 ) in the 10% FBS‐containing medium and allowed for cell adhesion for 2 days.…”

Section: Methodsmentioning

confidence: 99%

“…Then, the medium was removed, and the cells were washed with serum‐free DMEM (Gibco BRL) twice to remove serum components. After the medium was replaced with serum‐free DMEM (Gibco BRL), the cells were incubated under hypoxic conditions (3% O 2 ) to stimulate angiogenic factor secretion, and the CM was collected after 24 h. To remove cells from CM, the collected CM was centrifuged at 500 g for 10 min and filtered through a 0.22 µm filter (Corning Inc., Corning, NY).…”

Section: Methodsmentioning

confidence: 99%

“…Accordingly the angiogenic activity of tumor cell CM has been demonstrated in a number of studies. CM collected from the cultures of pulmonary carcinoma cells and fibrosarcoma cells enhanced the proliferation and tube formation of vascular endothelial cells in vitro . Herein, we evaluated the potential of tumor cell CM for therapeutic angiogenesis and ischemic disease treatment.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic angiogenesis using tumor cell‐conditioned medium

Jang

Kim

Han

et al. 2016

Biotechnology Progress

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Stem cell-conditioned medium (CM), which contains angiogenic factors that are secreted by stem cells, represents a potential therapy for ischemic diseases. Along with stem cells, tumor cells also secrete various angiogenic factors. Here, tumor cells as a cell source of CM for therapeutic angiogenesis was evaluated and the therapeutic efficacy of tumor cell CM in mouse hindlimb ischemia models was demonstrated. CM obtained from a human fibrosarcoma HT1080 cell line culture was compared with CM obtained from a human bone marrow-derived mesenchymal stem cell (MSC) culture. HT1080 CM contained higher concentrations of angiogenic factors compared with MSC CM, which was attributable to the higher cell density that resulted from a much faster growth rate of HT1080 cells compared with MSCs. For use in in vitro and in vivo angiogenesis studies, HT1080 CM was diluted such that HT1080 CM and MSC CM would have the same cell number basis. The two types of CMs induced the same extent of human umbilical vein endothelial cell (HUVEC) proliferation in vitro. The injection of HT1080 CM into mouse ischemic limbs significantly improved capillary density and blood perfusion compared with the injection of fresh medium. Although the therapeutic outcome of HT1080 CM was similar to that of MSC CM, the preparation of CM by tumor cell line culture would be much more efficient due to the faster growth and unlimited life-time of the tumor cell line. These data suggest the potential application of tumor cell CM as a therapeutic modality for angiogenesis and ischemic diseases. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:456-464, 2016.

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Conditioned media of carcinoma cells cultured in hypoxic microenvironment stimulate angiogenesis in vitro; relationship to basic fibroblast growth factor

Cited by 18 publications

References 44 publications

Hypoxia Induces FGF2 Production by Vascular Endothelial Cells and Alters MMP9 and TIMP1 Expression in Extravillous Trophoblasts and Their Invasiveness in a Cocultured Model

Hypoxia Induces FGF2 Production by Vascular Endothelial Cells and Alters MMP9 and TIMP1 Expression in Extravillous Trophoblasts and Their Invasiveness in a Cocultured Model

Hypoxia increases human keratinocyte motility on connective tissue.

Therapeutic angiogenesis using tumor cell‐conditioned medium

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