Expression of insulin-like growth factor II by a gastric carcinoma associated with hypoglycaemia

Horiuchi, Toshimitsu; Shinohara, Yoko; Sakamoto, Yoshimasa; Hizuka, Naomi; Watabe, Toshio; Mokuda, O; Tanaka, Kuniya; Shimizu, Nobuko; Sugano, Isamu; Nagao, Kouichi

doi:10.1007/bf00190569

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…An increased proportion of these higher molecular weight IGF-II forms has been reported in plasma and tissue extracts from patients with non-islet cell tumour hypoglycaemia (NICTH), a syndrome resulting from IGF-II overproduction by mesenchymal tumours of nonpancreatic origin (Daughaday et al 1988, Daughaday & Kapadia 1989). More recent reports have shown that IGF-II overexpression and pro-IGF-II forms are more widespread than first thought in various cancers (Horiuchi et al 1994, Singer et al 1995, Hodzic et al 1997, Van der Ven et al 1997).…”

Section: Introductionmentioning

confidence: 96%

Binding characteristics of pro-insulin-like growth factor-II from cancer patients: binary and ternary complex formation with IGF binding proteins-1 to -6

Bond¹,

Meka²,

Baxter³

2000

Journal of Endocrinology

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Many tumours secrete IGF-II in incompletely processed precursor forms. The ability of these pro-IGF-II forms to complex with the six IGF binding proteins (IGFBPs) is poorly understood. In this study, pro-IGF-II has been extracted from the serum and tumour tissue of two patients with non-islet cell tumour hypoglycaemia. These samples were used to study binary complex formation with IGFBPs-1 to -6 using competitive IGF-II binding assays and ternary complex formation with IGFBP-3 and IGFBP-5.In each case, IGFBPs-1 to -6 showed little difference in their ability to form binary complexes with recombinant IGF-II or tumour-derived pro-IGF-II forms, when the preparations were standardised according to IGF-II immunoreactivity. As previously described, ternary complex formation by acid-labile subunit (ALS) with IGFBP-3 and pro-IGF-II was greatly decreased compared with complex formation with mature IGF-II. In contrast, ALS bound similarly to IGFBP-5 in the presence of pro-IGF-II and mature IGF-II.These studies suggest that pro-IGF-II preferentially forms binary complexes with IGFBPs, and ternary complexes with IGFBP-5, rather than ternary complexes with IGFBP-3 as seen predominantly in normal serum. This may increase the tissue availability of serum pro-IGF-II, allowing its insulin-like potential to be realised.

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Section: Introductionmentioning

confidence: 96%

Binding characteristics of pro-insulin-like growth factor-II from cancer patients: binary and ternary complex formation with IGF binding proteins-1 to -6

Bond¹,

Meka²,

Baxter³

2000

Journal of Endocrinology

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“…A single subcutaneous injection of recombinant human IGF also can reduce blood potassium in short-term (15). In NICTH, however, hypokalemia was not generally recognized as a clinical symptom (6). In the present case, the reduction of blood potassium was closely related to the development of hypoglycemia.…”

Section: Figure 1 Advanced Liver Metastases By Abdominal Computed Tomentioning

confidence: 44%

“…Non-islet cell tumor hypoglycemia (NICTH) is a rare cause of hypoglycemia, and it is most commonly associated with large, slowgrowing, mesenchymal tumors located in the retroperitoneum or the thorax (2). Hypoglycemia associated with gastric cancer is rarely noted (3)(4)(5)(6), but its clinical manifestations remain to be explored. Here, we report a case of gastric cancer that first presented with hypokalemia, and subsequently developed uncontrollable hypoglycemia in association with multiple liver metastases.…”

Section: Introductionmentioning

confidence: 99%

Severe Hypoglycemia and Hypokalemia in Association with Liver Metastases of Gastric Cancer

et al. 2004

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“…Previous reports on IGF-2 concentrations in blood serum (31,41,49,58) and in tumour extracts (41,58) have demonstrated HMW forms of the IGF-2 peptide, similar to our findings. The demonstration of IGF-2 immunoreactive cells in NICTH cases (25,32,52) and of IGF-2 mRNA expression in tumour tissue extracts, as shown by Northern blots (16,17,25,52), gives further support to the idea of an actual synthesis of this IGF-2 peptide by the neoplastic cells. Our in situ hybridization results, and those in a recent report (1996) by Sohda & Yun (47), using the same technique, offer an additional piece of evidence for such a conclusion.…”

Section: Nicth Pathogenesismentioning

confidence: 78%

High‐molecular weight IGF‐2 expression in a haemangiopericytoma associated with hypoglycaemia

Höög

Nordqvist

Hulting

et al. 1997

APMIS

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Spontaneous hypoglycaemia is usually caused by an insulin‐producing islet‐cell tumour of the pancreas. Rarely, it can be caused by non‐islet cell tumours. Most of the tumours are of mesenchymal type, large, and slowly growing. One representative is haemangiopericytoma (HAP). The present report describes a case of a large recurrent retroperitoneal HAP associated with severe hypoglycaemia. Blood serum insulin and proinsulin concentrations were low. By means of acid‐gel chromatography and dot‐blot techniques, an increased amount of a high‐molecular‐weight IGF‐2 peptide was found. By using antigen retrieval procedures, IGF‐2‐immunoreactive tumour cells were found in specimens of the recent tumour recurrence ‐ but not in the original. When the in situ hybridization technique was used it could be shown that IGF‐2 mRNA labelling had already occurred in the original tumour specimen, 11 years before the onset of hypoglycaemic symptoms. These observations confirm the hypothesized hypoglycaemic effects of high‐molecular‐weight (HMW) IGF‐2, but also point to the presence of a prolonged compensation of this effect. A literature review, based on 17 similar cases of haemangiopericytoma with hypoglycaemia, is presented. Our observation and findings in the literature review support the idea that non‐islet‐cell tumour hypoglycaemia is caused by an overproduction of a HMW IGF‐2 peptide. The insulin‐like effect is mediated via non‐specific binding to the insulin receptors. To anticipate patients at risk of developing this kind of hypoglycaemia, the histopathological investigation should include not only immunohistochemical analyses of the presence of IGF‐2 peptide, but also in situ hybridization of the IGF‐2 mRNA expression.

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Expression of insulin-like growth factor II by a gastric carcinoma associated with hypoglycaemia

Cited by 7 publications

References 18 publications

Binding characteristics of pro-insulin-like growth factor-II from cancer patients: binary and ternary complex formation with IGF binding proteins-1 to -6

Binding characteristics of pro-insulin-like growth factor-II from cancer patients: binary and ternary complex formation with IGF binding proteins-1 to -6

Severe Hypoglycemia and Hypokalemia in Association with Liver Metastases of Gastric Cancer

High‐molecular weight IGF‐2 expression in a haemangiopericytoma associated with hypoglycaemia

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