Hypoxia increases human keratinocyte motility on connective tissue.

O’Toole, Edel A.; Marinkovich, M. Peter; Peavey, Christina; Amieva, Manuel R.; Furthmayr, Heinz; Mustoe, Thomas A.; Woodley, David T.

doi:10.1172/jci119837

Cited by 115 publications

(106 citation statements)

References 68 publications

(99 reference statements)

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“…Although such an association was not confirmed overall, analysis in the group of patients with poor vascularization showed a significant association of HIF2α expression with c-erbB-2 overexpression (P = 0.04, data not shown). C-erbB-2 is involved in epithelial cell migration and hypoxia has been shown to induce keratinocyte motility (de-Porter et al, 1994;O'Toole et al, 1997). Whether HIF expression activates migration-related pathways is unknown, but the observed association of HIF2α expression with c-erbB-2 supports our previous findings that c-erbB-2 defines a group of poorly vascularized tumours associated with poor prognosis (Giatromanolaki et al, 1996).…”

Section: Hif1α/2α Expression In Nsclc 887supporting

confidence: 69%

Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival

et al. 2001

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Summary Hypoxia inducible factors HIF1α and HIF2α are important proteins involved in the regulation of the transcription of a variety of genes related to erythropoiesis, glycolysis and angiogenesis. Hypoxic stimulation results in rapid increase of the HIF1α and 2α protein levels, as a consequence of a redox-sensitive stabilization. The HIFαs enter the nucleus, heterodimerize with the HIF1β protein, and bind to DNA at the hypoxia response elements (HREs) of target genes. In this study we evaluated the immunohistochemical expression of these proteins in 108 tissue samples from non-small-cell lung cancer (NSCLC) and in normal lung tissues. Both proteins showed a mixed cytoplasmic/nuclear pattern of expression in cancer cells, tumoural vessels and tumour-infiltrating macrophages, as well as in areas of metaplasia, while normal lung components showed negative or very weak cytoplasmic staining. Positive HIF1α and HIF2α expression was noted in 68/108 (62%) and in 54/108 (50%) of cases respectively. Correlation analysis of HIF2α expression with HIF1α expression showed a significant association (P < 0.0001, r = 0.44). A strong association of the expression of both proteins with the angiogenic factors VEGF (P < 0.004), PD-ECGF (P < 0.003) and bFGF (P < 0.04) was noted. HIF1α correlated with the expression of bek-bFGF receptor expression (P = 0.01), while HIF2α was associated with intense VEGF/KDR-activated vascularization (P = 0.002). HIF2α protein was less frequently expressed in cases with a medium microvessel density (MVD); a high rate of expression was noted in cases with both low and high MVD (P = 0.006). Analysis of overall survival showed that HIF2α expression was related to poor outcome (P = 0.008), even in the group of patients with low MVD (P = 0.009). HIF1α expression was marginally associated with poor prognosis (P = 0.08). In multivariate analysis HIF2α expression was an independent prognostic indicator (P = 0.006, t-ratio 2.7). We conclude that HIF1α and HIF2α overexpression is a common event in NSCLC, which is related to the up-regulation of various angiogenic factors and with poor prognosis. Targeting 881-890 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2001.2018, available online at http://www.idealibrary.com on http://www.bjcancer.comIn the present study we examined the expression patterns of HIF1α and of HIF2α in normal lung and in a series of non-smallcell lung carcinomas. The expression of HIFs was analysed in comparison with the microvessel density, with the expression of multiple angiogenic factors and receptors as well as with the expression of onco-proteins, previously shown to have a role in lung cancer. The prognostic role of HIF expression was also studied. MATERIALS AND METHODSWe examined 108 tumour samples from patients with early operable (T1,2-N0,1-M0 staged) non-small-cell lung cancer (72 squamous and 36 adenocarcinomas). 12 samples from normal lung obtained during thoracic surgery for reasons other than lung cancer were also examined. Histological diagnosis, grading and Nstage w...

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Section: Hif1α/2α Expression In Nsclc 887supporting

confidence: 69%

Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival

et al. 2001

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“…In our experiments only transient stimulation of migration was observed by egg-oil, but in healing tissue hypoxia is present which may activate this migration (22) and increased oxygen consumption due to partial uncoupling may further support this effect.…”

Section: Discussionsupporting

confidence: 46%

Cellular Responses to Egg-Oil (Charismon©)

Bereiter‐Hahn

Bernd

Beschmann

et al. 2014

Acta Med. (Hradec Kralove, Czech Repub.)

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Summary: Egg-oil (Charismon © ) is known for its beneficial action in wound healing and other skin irritancies and its antibacterial activity. The physiological basis for these actions has been investigated using cells in culture: HaCaT-cells (immortalized human keratinocytes), human endothelial cells in culture (HUVEC), peripheral blood mononuclear lymphocytes (PBML) and a full thickness human skin model (FTSM). Emphasis was on the influence of egg-oil on cell migration and IL-8 production in HaCaT cells, respiration, mitochondrial membrane potential, reactive oxygen (ROS) production and proliferation in HUVEC and HaCaT cells, cytokine and interleukin production in PBML and UV-light induced damage of FTSM. IL-8 production by HaCaT cells is stimulated by egg-oil whilst in phythemagglutinin-activated PBMLs production of the interleukins IL-2, IL-6, IL-10 and IFN-γ and TFN-α is reduced. ROS-production after H 2 O 2 stimulation first is enhanced but later on reduced. Respiration becomes activated due to partial uncoupling of the mitochondrial respiratory chain and proliferation of HaCaT and HUVEC is reduced. Recovery of human epidermis cells in FTSM after UV-irradiation is strongly supported by egg-oil. These results support the view that egg-oil acts through reduction of inflammatory processes and ROS production. Both these processes are equally important in cellular aging as in healing of chronic wounds.

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“…These results appear to be in conflict with earlier studies. However, those studies evaluated the effect of acute hypoxia on keratinocytes, which may indeed be stimulatory instead of inhibitory [48]. The role of oxygen in collagen fibrillogenesis has been previously documented [5].…”

Section: Discussionmentioning

confidence: 99%

Integration of Blood Outgrowth Endothelial Cells in Dermal Fibroblast Sheets Promotes Full Thickness Wound Healing

et al. 2010

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Vascularization is the cornerstone of wound healing. We introduced human blood outgrowth endothelial cells (hBOEC) in a self-assembled human dermal fibroblast sheet (hDFS), intended as a tissue-engineered dermal substitute with inherent vascular potential. hBOEC were functionally and molecularly different from early endothelial progenitor cells and human umbilical vein endothelial cells (HUVEC). hBOEC alone, unlike HUVEC, efficiently revascularized and re-oxygenated the wound bed, both by active incorporation into new vessels and by trophic stimulation of host angiogenesis in a dose-dependent manner. Furthermore, hBOEC alone, but not HUVEC, accelerated epithelial coverage and matrix organization of the wound bed. In addition, integration of hBOEC in hDFS not only further improved vascularization, epithelial coverage and matrix organization but also prevented excessive wound contraction. In vitro analyses with hBOEC, fibroblasts and keratinocytes revealed that these effects were both due to growth factor crosstalk and to short cutting hypoxia. Among multiple growth factors secreted by hBOEC, placental growth factor mediated at least in part the beneficial effects on keratinocyte migration and proliferation. Overall, this combined tissue engineering approach paves the way for clinical development of a fully autologous vascularized dermal substitute for patients with large skin defects that do not heal properly.

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Hypoxia increases human keratinocyte motility on connective tissue.

Cited by 115 publications

References 68 publications

Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival

Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival

Cellular Responses to Egg-Oil (Charismon©)

Integration of Blood Outgrowth Endothelial Cells in Dermal Fibroblast Sheets Promotes Full Thickness Wound Healing

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