Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor

Ishikawa, Fuyuki; Miyazono, Kohei; Hellman, Ulf; Drexler, Hannes C.A.; Wernstedt, Christer; Hagiwara, Koichi; Usuki, Kensuke; Takaku, Fumimaro; Risau, Werner; Heldin, Carl‐Henrik

doi:10.1038/338557a0

Cited by 661 publications

(376 citation statements)

References 30 publications

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“…Although platelet-derived endothelial cell growth factor was initially cloned as a novel non-heparin-binding angiogenic factor present in platelets, this factor was subsequently shown to be TP (Ishikawa et al, 1989;Usuki et al, 1989;Moghaddam et al, 1992). recently showed that TP is angiogenic in the rat subcutaneous sponge model, its activity being independent of basic FGF.…”

Section: Discussionmentioning

confidence: 99%

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

Koukourakis

Giatromanolaki²,

Kakolyris³

et al. 1998

Br J Cancer

113

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Summary Angiogenesis is recognized as an important step in tumour pathogenesis that is related to invasion and metastatic spread and which consequently results in poor clinical outcome. In this study, we have examined the role of tumour stroma-activated fibroblasts and macrophage infiltration in the development of the angiogenic and metastatic phenotype in non-small-cell lung cancer (NSCLC). A total of 141 cases of early stage I-Il NSCLC treated with surgery alone were analysed. The JC-70 (anti-CD31) MAb was used for the assessment of vascular grade. The P-GF.44C MAb was used to assess thymidine phosphorylase (TP) reactivity in cancer cells, stromal fibroblasts and macrophages. Cancer cell TP overexpression related to high vascular grade and to advanced T stage (P = 0.0004 and P = 0.02). Expression of TP in stromal fibroblasts also correlated with high angiogenesis (P = 0.01), but was independent of cancer cell expression. Fibroblast TP overexpression was related to abundant stroma (P = 0.003), suggesting that TP may be a marker of active stroma. Moreover, intense macrophage infiltration was associated with fibroblast TP reactivity, regardless of the amount of stroma, suggesting that macrophages may be a major contributor to TP expression in stroma. Survival analysis showed that cancer cell TP overexpression was related to poor prognosis (P = 0.005). Although stroma TP is related to angiogenesis, in the low vascular grade group it defined a group of patients with better prognosis (P = 0.02). It may be that fibroblast TP reactivity is an indirect marker of tumour infiltration by functional macrophages, which have an antitumour effect. We conclude that stromal macrophage and fibroblast TP reactivity may have an important role in non-small-cell lung cancer behaviour. Understanding the role of stromal fibroblasts and inflammatory cells and their interaction with oncoprotein expression is essential for the elucidation of lung cancer pathogenesis.

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Section: Discussionmentioning

confidence: 99%

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

Koukourakis

Giatromanolaki²,

Kakolyris³

et al. 1998

Br J Cancer

113

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“…In various in vitro studies, TP had a chemotactic effect on endothelial cells [5,6,7,8]. In vivo, TP induced angiogenesis using various cancer cell lines that were transfected with TP [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, dR induced endothelial cell migration in various studies [5,8]. The association between TP activity and angiogenesis is based on the potential accumulation of TdR-derived sugars.…”

mentioning

confidence: 99%

Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells

Bijnsdorp

Azijli

Jansen

et al. 2010

Biochemical Pharmacology

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“…A variety of proteins such as the vascular endothelial growth factor, the platelet-derived endothelial cell growth factors and the basic fibroblast growth factor released by tumour and stroma cells have been recognised to be potent inducers of angiogenesis (Bikfalvi et al, 1997;Ishikawa et al, 1989;Ferrara, 2000).…”

mentioning

confidence: 99%

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

et al. 2002

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In order to determine whether angiogenesis is a prognostic marker in lung cancer, we performed a systematic review of the literature to assess the prognostic value on survival of microvessel count in patients with lung cancer. Published studies were identified by an electronic search in order to aggregate survival results, after a methodological assessment using a quality scale designed by the European Lung Cancer Working Party. To be eligible, a study had to deal with microvessel count assessment in lung cancer patients on the primary site and to provide survival analysis according to microvessel count expression. Microvessel count has been assessed on surgical samples by immunohistochemistry using factor VIII in 14 studies, CD34 in 10 and CD31 in eight. Respectively 1866, 1440 and 1093 non-small cell lung cancer patients were considered. The overall median quality scores were respectively 52, 59 and 59% for studies assessing microvessel count via factor VIII, CD34 and CD31, without significant difference between studies evaluable or not for meta-analysis nor between studies with significant or non significant results. Seven 'factor VIII' studies, nine 'CD34' and seven 'CD31' provided sufficient data allowing a metaanalysis on survival and were evaluable for results aggregation. This showed that a high microvessel count in the primitive lung tumour was a statistically significant poor prognostic factor for survival in non small cell lung cancer whatever it was assessed by factor VIII (HR: 1.81; 95% CI: 1.16 -2.84), CD34 (HR: 1.99; 95% CI: 1.53 -2.58) or CD31 (HR: 1.80; 95% CI: 1.10 -2.96). Variations in survival among the individual studies can be explained in addition to patients selection criteria by the heterogeneous methodologies used to stain and count microvessels: different antibody clones, identification of 'hotspots', Weidner or Chalkey counting method, cut-off selection. Microvessel count, reflecting the angiogenesis, appears to be a poor prognostic factor for survival in surgically treated non small cell lung cancer but standardisation of angiogenesis assessment by the microvessel count is necessary.

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Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor

Cited by 661 publications

References 30 publications

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

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

Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

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