Different patterns of stromal and cancer cell thymidine phosphorylase reactivity in non-small-cell lung cancer: impact on tumour neoangiogenesis and survival

Koukourakis, Michael I.; Giatromanolaki, Alexandra; Kakolyris, S; O’Byrne, Kenneth J.; Apostolikas, N.; Skarlatos, John; Gatter, Kevin C.; Harris, Adrian L.

doi:10.1038/bjc.1998.280

Cited by 113 publications

(86 citation statements)

References 26 publications

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“…The role of immune response in cancer progression seems to be possibly dual and remains not well elucidated (Chambers et al, 1997;Jonjic et al, 1998;Koukourakis et al, 1998;Toi et al, 1999;Shimura et al, 2000). Indeed, despite the role of monocytes/ macrophages in host defence, previous studies have suggested a potential deleterious effect of stroma-localised monocytes/macrophage, in relation with enhanced angiogenesis ( Urokinase is visualised as a transparent lysis area of the gel after 36 h. Two lysis areas were observed with purified u-PA, one at 55 kDa molecular weight and a minor one corresponding to the low molecular weight u-PA at 35 kDa.…”

Section: Discussionmentioning

confidence: 99%

Cooperation between monocytes and breast cancer cells promotes factors involved in cancer aggressiveness

Blot

Chen

Vasse³

et al. 2003

Br J Cancer

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In breast cancers, clinical symptoms of inflammation localised around the tumour at the time of diagnosis have been considered to have poor prognosis significance. In this study, the biological mechanisms responsible for the deleterious action of monocytes in cancer were investigated. The incubation of the breast-cancer-derived MDA-MB231 cells with monocytes resulted in an increase in factors involved in cell invasion (i.e. both cancer cells and monocytes-associated urokinase and Tissue Factor, and PAI-1 and MMP-9 secretion). Moreover, the functions of monocytes were also modified. Incubation of monocytes with MDA-MB231 cancer cells resulted in a downregulation in the secretion of the antiproliferative cytokine Oncostatin M, while the apoptotic factor TNF alpha was dramatically increased. However, MDA-MB231 cancer cells have been shown to be resistant towards the apoptotic action of TNF alpha. These findings demonstrate that incubation of MDA-MB231 cancer cells with monocytes induced a crosstalk, which resulted in an increased expression of factors involved in cancer cell invasiveness and in a modification of monocytes function against cancer cells, while inflammatory effects were increased. British Journal of Cancer (2003) The importance of stroma in cancer formation, growth and dissemination is now well established. In order to generate an invasive tumour, cancer cells need several mutations, but also formally necessitate sustenance from noncancer stroma cells, which supply and permit cancer cell growth and invasion. The presence of cytokines and inflammatory cells in cancer stroma, indicating defence reaction against cancer, generally correspond to a poor prognosis (Kleer et al, 2000). Furthermore, in breast cancer, initial presentation with clinical symptoms of inflammation indicates a particular aggressiveness and a worst prognosis than other breast cancers (Chevallier, 1993;Palangie et al, 1994;Kleer et al, 2000). However, the mechanisms leading to the pathological action of stroma-localised inflammatory cells in cancer, such as monocytes, remain poorly understood.The current study was undertaken to explore whether the factors of aggressiveness expressed by cancer cells were modified in the presence of monocytes. We also analysed the consequences of the incubation of monocytes with MDA-MB231 cancer cells on functions of monocytes both in the defence against tumour cells and in inflammatory functions. For this purpose, we tested the consequences of the interaction of the highly invasive breastderived MDA-MB231 cancer cells with monocytes with an in vitro system. MATERIAL AND METHODS Monocytes isolationA measure of 80 mm of blood from healthy volunteers was collected in sterile polypropylene tubes (Costar, Cambridge, MA, USA) containing 7.5 ml of ACD (38 mM citric acid, 74 mM citrate and 136 mM glucose). Platelet-rich plasma was removed by centrifugation (10 min, 100 g at room temperature). Mononuclear cells were collected after centrifugation (45 min, 400 g at room temperature) in Leucosep tubes (Costar, C...

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Section: Discussionmentioning

confidence: 99%

Cooperation between monocytes and breast cancer cells promotes factors involved in cancer aggressiveness

Blot

Chen

Vasse³

et al. 2003

Br J Cancer

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“…14 -24 Several investigators 20 -24 have focused on tumor cell-TP expression in NSCLC. In addition, Koukourakis et al 21 reported stromal cell-TP expression and tumor cell-TP expression in NSCLC, indicating that stromal fibroblasts intensively express TP in a number of NSCLCs. Intensive TP expression has been observed in intratumoral macrophages of colorectal, gastric, and breast carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…TP expression has been observed in tumor cells of nonsmall cell lung carcinoma (NSCLC). 20 -24 Koukourakis et al 21 reported different patterns of stromal and tumor cell-TP expression in NSCLC. The clinicopathologic significance of TP expression in tumor cells and/or stromal cells in NSCLC has remained unclear.…”

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confidence: 99%

Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma

Kojima

Shijubo

Abe

2002

Cancer

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Sleeping giants: As a mimic of cell agglomeration to form tissues, a novel vesicle aggregation process with the characteristic advantages of being highly efficient, light‐responsive, reversible, large‐scale, and stable is reported. Giant hyperbranched polymer vesicles (5–10 μm) are used as the building blocks (see scheme), and the vesicle aggregates can assemble and disassemble with alternating UV and Vis irradiation.

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“…We suggest that although hypoxia triggers the expression of a cascade of angiogenic factors through HIF stabilization, the process of angiogenesis is subject to other modulators. Strong expression of endogenous inhibitors of angiogenesis produced by cancer or stromal cells may therefore counter the effectiveness of the angiogenic cascade released by HIFs (Dong et al, 1997;Koukourakis et al, 1998), while a moderate vascularization may be enough for the restoration of oxygenation that may bring the HIF levels close to the normal level. HIF levels are normalized within minutes after the restoration of oxygenation (Wiesner et al, 1998).…”

Section: Hif1α/2α Expression In Nsclc 887mentioning

confidence: 99%

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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Different patterns of stromal and cancer cell thymidine phosphorylase reactivity in non-small-cell lung cancer: impact on tumour neoangiogenesis and survival

Cited by 113 publications

References 26 publications

Cooperation between monocytes and breast cancer cells promotes factors involved in cancer aggressiveness

Cooperation between monocytes and breast cancer cells promotes factors involved in cancer aggressiveness

Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma

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

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