Prognostic significance of the expression of vascular endothelial growth factors A, B, C, and D and their receptors R1, R2, and R3 in patients with nonsmall cell lung cancer

Pau, Enrique Carrillo de Santa; Arias, F.; Peláez, E. Caso; Muñoz-Molina, Gemma María; Hernández, Ignacio Sánchez; Trueba, Ignacio Muguruza; Balsalobre, Ramón Moreno; Sacristán, Silvia; Pinillos, A. Gómez; Lobo, María del Val Toledo

doi:10.1002/cncr.24193

Cited by 91 publications

(48 citation statements)

References 54 publications

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“…In particular, it has been demonstrated that FLNA physically interacts with HIF-1a (Zhenga et al 2014), that regulates angiogenesis through upregulation of vascular endothelial growth factor (VEGF) (Uramoto et al 2010, Berardi et al 2011, Semenza 2012. Whereas VEGF-driven angiogenesis may play an important role in endocrine tumourigenesis and tumour progression (Hanahan et al 1996) and several in vitro studies suggested that SS analogues display potent antiangiogenic properties (Woltering et al 1991, Barrie et al 1993, Danesi & Del Tacca 1996, Kumar et al 2004, we showed that SST2 agonist reduced VEGF protein levels and release, but this inhibitory effect was totally abolished in the absence of FLNA.…”

Section: Discussionmentioning

confidence: 71%

“…In fact, a positive relationship between FLNA and vascular endothelial growth factor (VEGF) was found in patients with lung cancer (Uramoto et al 2010), suggesting that FLNA is implicated in angiogenesis through links with VEGF. Interestingly, it has been demonstrated that VEGF pathway is overexpressed in neuroendocrine tumours (Ö berg et al 2013), this pathway being inhibited by somatostatin analogues (Villaume et al 2010).…”

Section: Introductionmentioning

confidence: 99%

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Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours

Vitali

Cambiaghi

Zerbi

et al. 2016

Endocrine-Related Cancer

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Somatostatin receptor type 2 (SST2) is the main pharmacological target of somatostatin (SS) analogues widely used in patients with pancreatic neuroendocrine tumours (P-NETs), this treatment being ineffective in a subset of patients. Since it has been demonstrated that Filamin A (FLNA) is involved in mediating GPCR expression, membrane anchoring and signalling, we investigated the role of this cytoskeleton protein in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in human P-NETs and in QGP1 cell line. We demonstrated that FLNA silencing was not able to affect SST2 expression in P-NET cells in basal conditions. Conversely, a significant reduction in SST2 expression (K43G21%, P!0.05 vs untreated cells) was observed in FLNA silenced QGP1 cells after long term SST2 activation with BIM23120. Moreover, the inhibitory effect of BIM23120 on cyclin D1 expression (K46G18%, P!0.05 vs untreated cells), P-ERK1/2 levels (K42G14%; P!0.05 vs untreated cells), cAMP accumulation (K24G3%, P!0.05 vs untreated cells), VEGF expression (K31G5%, P!0.01 vs untreated cells) and in vitro release (K40G24%, P!0.05 vs untreated cells) was completely lost after FLNA silencing. Interestingly, BIM23120 promoted cell adhesion (C86G45%, P!0.05 vs untreated cells) and inhibited cell migration (K24G2%, P!0.00001 vs untreated cells) in P-NETs cells and these effects were abolished in FLNA silenced cells. In conclusion, we demonstrated that FLNA plays a crucial role in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in P-NETs and in QGP1 cell line, suggesting a possible role of FLNA in determining the different responsiveness to SS analogues observed in P-NET patients.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours

Vitali

Cambiaghi

Zerbi

et al. 2016

Endocrine-Related Cancer

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“…Furthermore, VEGFR-1 is usually considered to function as a decoy receptor for VEGF, and it is not markedly phosphorylated upon VEGF binding (36). The prognostic role of VEGFR-1 in tumors has remained controversial (37,38). In the search for novel anticancer treatments, some of the new smallmolecule tyrosine kinase inhibitors are, however, designed also to inhibit VEGFR-1 (17).…”

Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Färkkilä¹,

Anttonen²,

Pociuviene³

et al. 2011

European Journal of Endocrinology

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Objective: Ovarian granulosa cell tumors (GCTs) are hormonally active sex cord stromal tumors accounting for 3-5% of all ovarian cancers. These tumors are generally diagnosed at an early stage but there is a high risk of recurrence, associated with high mortality. Treatment of recurrent GCTs is difficult, and biologically targeted treatment modalities are lacking. GCTs are highly vascularized, and angiogenic factors most probably play a role in their pathology. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis, but in GCTs, the role of VEGF and its receptors VEGFR-1 (FLT1) and VEGFR-2 (KDR) remains largely unknown. Our objective is to study the expression of VEGF and its receptors in human GCTs. Methods: We analyzed GCTs from 106 patients for the expressions of VEGF and its receptors utilizing tumor tissue microarray, tumor mRNA, and patient serum samples. Results: We found that VEGF and its main biologically active receptor VEGFR-2 were highly expressed in primary and recurrent GCTs, when compared with normal granulosa-lutein cells. The expression of VEGF correlated positively to tumor microvessel density and to VEGFR-2 expression at the protein (P!0.05) and mRNA (P!0.05) levels. In contrast to VEGFR-2, the expression of VEGFR-1 was weak. Tumor VEGF protein expression was not prognostic for recurrence, however, we found high levels of circulating VEGF in the serum of patients with primary GCT. Conclusions:The results suggest an important role of VEGF and VEGFR-2 in GCT pathology and support the possibility of applying novel VEGF-or VEGFR-2-targeted treatments to patients with GCT.

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“…Positive VEGF immunostaining independently predicts poor prognosis in gastric cancer patients. Strong VEGF staining showed a significant correlation with both short time of relapse and short survival in NSCLC [18]. Increased expression is also a prognostic marker in papillary thyroid carcinoma.…”

Section: Angiogenesis Markersmentioning

confidence: 95%

Role of Pathology and Immunohistochemistry in the New Era Of Molecular Therapy

Ahmed¹

2010

TOPROCJ

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Abstract:The modern practice of pathology entails increasing involvement with management of cancer patients. Pathologists are often faced with clinical and research involvements that obligate them to search for prognostic and therapeutic markers on patients' tumor samples. A practical example would be the detection of HER2-neu in breast cancer which has revolutionized the use of prognostic-therapeutic immunohistochemistry (IHC) in the practical management of patients. Numerous other markers and proliferation pathways have recently been elucidated in many human cancers including pediatric cancers. Although most of these markers are being detected by conventional molecular techniques, IHC methods, routinely practiced in histopathologic laboratories, are being employed at an increasing pace. Since most of these proliferation markers are also the targets of new specific therapy, their positive identification often correlates with the appropriateness of that specific therapy and with other parameters that can gauge the patient's prognosis. A good example is the identification of epidermal growth factor receptor by IHC in the patient's lung tumor as an indicator of the tumor responsiveness to "Gefitinib". Such potential application of immunohistochemistry in patients' care necessitates adequate standardization of this technique to optimize patients' management, since erroneous results can lead to erroneous management of patients with cancer. These facts will initiate a new role for pathology laboratory departments to provide a stronger impact on patients' managements.

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Prognostic significance of the expression of vascular endothelial growth factors A, B, C, and D and their receptors R1, R2, and R3 in patients with nonsmall cell lung cancer

Cited by 91 publications

References 54 publications

Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours

Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Role of Pathology and Immunohistochemistry in the New Era Of Molecular Therapy

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