Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours

Wulbrand, Ulrich; Wied, M.; Zöfel, P.; Göke, Burkhard; Arnold, R.; Fehmann, Hans-Christoph

doi:10.1046/j.1365-2362.1998.00397.x

Cited by 102 publications

(96 citation statements)

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“…Only two studies have so far investigated c-Met expression in NE GI tumours. Wulbrand et al (1998) found the cMet mRNA expression frequencies to vary considerably, with the highest found in gastrinomas (33%) and the lowest (11%) in small intestine carcinoid tumours. In a gastrinoma study (Peghini et al, 2002), universal expression of c-Met mRNA was demonstrated in all 22 tumours investigated.…”

Section: Hgf- Egf-and Pacap-induced Proliferationmentioning

confidence: 97%

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Identification of novel growth factor-responsive genes in neuroendocrine gastrointestinal tumour cells

et al. 2005

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Targeting growth-regulatory pathways is a promising approach in cancer treatment. A prerequisite to the development of such therapies is characterisation of tumour growth regulation in the particular tumour cell type of interest. In order to gain insight into molecular mechanisms underlying proliferative responses in neuroendocrine (NE) gastrointestinal (GI) tumours, we investigated gene expression in human carcinoid BON cells after exposure to gastrin, hepatocyte growth factor (HGF), pituitary adenylate cyclaseactivating polypeptide or epidermal growth factor. We particularly focused on gastrin-and HGF-induced gene expression, and identified 95 gastrin-and 101 HGF-responsive genes. The majority of these genes are known mediators of processes central in tumour biology, and a number of them have been associated with poor prognosis and metastasis in cancer patients. Furthermore, we identified 12 genes that were regulated by all four factors, indicating that they may be universally regulated during NE GI tumour cell proliferation. Our findings provide useful hypotheses for further studies aimed to search for new therapeutic targets as well as tumour markers in NE GI tumours.

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Section: Hgf- Egf-and Pacap-induced Proliferationmentioning

confidence: 97%

“…The EGF receptor is found (over)expressed in various human NE tumours (Nilsson et al, 1995;Wulbrand et al, 1998;Peghini et al, 2002), including GI carcinoids. More recently, the EGFR tyrosine kinase inhibitor gefitinib has been shown to inhibit growth of various NE GI tumour cells, including human carcinoid BON cells (Höpfner et al, 2003).…”

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confidence: 99%

Identification of novel growth factor-responsive genes in neuroendocrine gastrointestinal tumour cells

et al. 2005

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“…It has been shown that BON1 cells and tissue specimens of SI-NETs express the transcripts of all three TGFβs (β1, β2 and β3) and both receptors (TGFβR1 and TGFβR2) (Beauchamp et al 1991, Chaudhry et al 1994, Wulbrand et al 1998, Wimmel et al 2003. The expression of TGFβ isoforms differs between tissue components with all three isoforms being present in tumour tissue, but only TGFβ2 showed strong IHC staining in stroma .…”

Section: Figurementioning

confidence: 99%

“…In vitro, FGF2 is shown to be expressed by BON1 cells and to stimulate proliferation of these cells (Beauchamp et al 1991). FGF receptors are found in most SI-NETs, both in tumour and stromal cells (Facco et al 1998, Wulbrand et al 1998. Although the presence of FGF2 in tumour cells and stroma suggests involvement in cellular processes of the TME, the effect of FGF2 on tumour development remains uncertain.…”

Section: Basic Fibroblast Growth Factor (Fgf2)mentioning

confidence: 99%

“…The expression of EGFR detected in SI-NETs differs vastly between studies, ranging from 33 to 100% (Nilsson et al 1995, Krishnamurthy & Dayal 1997, Wulbrand et al 1998, Shah et al 2006. In 2006, Shah and colleagues analysed 98 NETs, of which 42 were from midgut origin, for the presence of EGFR.…”

Section: Transforming Growth Factor Alpha (Tgfα) and Epidermal Growthmentioning

confidence: 99%

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Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum

Blažević¹,

Hofland²,

Hofland³

et al. 2018

Endocrine-Related Cancer

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Small intestinal neuroendocrine tumours (SI-NETs) are neoplasms characterized by their ability to secrete biogenic amines and peptides. These cause distinct clinical pathology including carcinoid syndrome, marked by diarrhoea and flushing, as well as fibrosis, notably mesenteric fibrosis. Mesenteric fibrosis often results in significant morbidity by causing intestinal obstruction, oedema and ischaemia. Although advancements have been made to alleviate symptoms of carcinoid syndrome and prolong the survival of patients with SI-NETs, therapeutic options for patients with mesenteric fibrosis are still limited. As improved insight in the complex pathogenesis of mesenteric fibrosis is key to the development of new therapies, we evaluated the literature for known and putative mediators of fibrosis in SI-NETs. In this review, we discuss the tumour microenvironment, growth factors and signalling pathways involved in the complex process of fibrosis development and tumour progression in SI-NETs, in order to elucidate potential new avenues for scientific research and therapies to improve the management of patients suffering from the complications of mesenteric fibrosis.

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A novel somatostatin conjugate with a high affinity to all five somatostatin receptor subtypes

Wulbrand

Feldman

Pfestroff

et al. 2002

Cancer

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BACKGROUND Somatostatin receptors (SRS, five subtypes) are expressed in a variety of human tumors, including most tumors of neuroendocrine origin, breast tumors, certain brain tumors, renal cell tumors, lymphomas, and prostate cancer. Somatostatin (SMS) triggers cytostatic and cytotoxic effects and has a general inhibitory effect on secretion mediated through its interaction with SRS. That is the basis for its use in the treatment of SRS‐positive tumors. Radiolabeled SMS analogs can also be used for systemic radiotherapy and for diagnostic investigations. METHODS Sms‐14 was conjugated to a periodate‐activated dextran70 (mean molecular weight, 70 kD) by reductive amination. The human tumor cell line LCC‐18, from a neuroendocrine colonic tumor, was used for stable transfection with each SRS gene separately; transfection was achieved with the expression system TETon (Clontech, Palo Alto, CA). Clones were selected by culturing with G418 and hygromycin B, and positive clones were identified by reverse transcriptase–polymerase chain reaction and binding of iodine‐125–labeled SMS‐14. The binding affinity for each SRS subtype was then determined for the SMS‐dextran conjugate (with SMS‐14 used as a positive control). RESULTS Sms‐dextran70 showed high affinity binding to all five receptor subtypes. The IC50 values were between 3 and 80 nM. CONCLUSIONS This conjugate has a long circulation half‐life (i.e., ≈27 hours after subcutaneous administration in mice) and, with high SRS pan‐affinity demonstrated in this study, it has potential in the therapy of SRS‐positive tumors. Currently, the clinical significance of SMS‐dextran70 is being explored in a clinical Phase I–II study of patients with hormone‐refractory prostate cancer. The outcome of this study will be reported when it is available. Cancer 2002;94:1293–7. © 2002 American Cancer Society. DOI 10.1002/cncr.10299

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Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours

Abstract: In spite of the common cellular origin of these tumours, differences in growth factor receptor expression suggest the existence of different pathways during tumour subtype development.

Cited by 102 publications

References 50 publications

Identification of novel growth factor-responsive genes in neuroendocrine gastrointestinal tumour cells

Identification of novel growth factor-responsive genes in neuroendocrine gastrointestinal tumour cells

Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum

A novel somatostatin conjugate with a high affinity to all five somatostatin receptor subtypes

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