PRESENCE OF IGF-I IN HUMAN MIDGUT CARCINOID-TUMORS - AN AUTOCRINE REGULATOR OF CARCINOID-TUMOR GROWTH

被引:64
作者
NILSSON, O
WANGBERG, B
THEODORSSON, E
SKOTTNER, A
AHLMAN, H
机构
[1] SAHLGRENS UNIV HOSP, DEPT SURG, S-41345 GOTHENBURG, SWEDEN
[2] KAROLINSKA HOSP, DEPT CLIN CHEM, S-10401 STOCKHOLM 60, SWEDEN
[3] KABI PEPTIDE HORMONES, STOCKHOLM, SWEDEN
关键词
D O I
10.1002/ijc.2910510206
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The presence of IGF-I and IGF-I receptors in human midgut carcinoid tumours has been investigated. Using immunocyto-chemistry, IGF-1-positive tumour cells were demonstrated in 11/11 tumour cases studied. Labelling of consecutive sections with antibodies against IGF-I and proliferating cell nuclear antigen (PCNA)/cyclin demonstrated a co-distribution of the 2 antigens in carcinoid tumours. Extracts of tumour tissues were subjected to radioimmunoassay and shown to contain significant amounts of IGF-1. Reverse-phase HPLC of tumour extracts demonstrated a major IGF-1-immunoreactive component eluting in the position of rhlGF-1, but also 2 other more hydrophobic forms. Conditioned serum-free media from primary cultures of carcinoid tumors contained detectable amounts of IGF-I, indicating a spontaneous release of IGF-I from tumour cells into the culture medium. Levels of IGF-I in media were reduced (19%) after incubation of cultures with a somatostatin analogue for 4 days. IGF-I receptors were observed on tumour cells in 4/10 tumours by immunocytochemistry. Tumour cells with immunoreactive IGF-I receptors could be stimulated to enhanced growth, measured as an increase in DNA contents, by exogenous administration of IGF-I every 3-4 days for 2 weeks. The results show that cultured human midgut carcinoid tumours secrete IGF-I and that some of the tumours also have IGF-I receptors. We therefore suggest that IGF-I may act as an autocrine or paracrine regulator of carcinoid tumour-cell growth.
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页码:195 / 203
页数:9
相关论文
共 36 条
[21]  
LU J, 1989, CANCER RES, V49, P4963
[22]   REGULATION OF INSULIN-LIKE GROWTH FACTOR-I GENE-EXPRESSION BY GROWTH-HORMONE [J].
MATHEWS, LS ;
NORSTEDT, G ;
PALMITER, RD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (24) :9343-9347
[23]   INSULIN-LIKE GROWTH FACTOR-I CAN MEDIATE AUTOCRINE PROLIFERATION OF HUMAN SMALL CELL LUNG-CANCER CELL-LINES INVITRO [J].
NAKANISHI, Y ;
MULSHINE, JL ;
KASPRZYK, PG ;
NATALE, RB ;
MANECKJEE, R ;
AVIS, I ;
TRESTON, AM ;
GAZDAR, AF ;
MINNA, JD ;
CUTTITTA, F .
JOURNAL OF CLINICAL INVESTIGATION, 1988, 82 (01) :354-359
[24]  
OHMURA E, 1990, CANCER RES, V50, P103
[25]   RAPID AND SIMPLE METHOD FOR THE DETERMINATION OF PICOGRAM LEVELS OF SEROTONIN IN BRAIN-TISSUE USING LIQUID-CHROMATOGRAPHY WITH ELECTROCHEMICAL DETECTION [J].
PONZIO, F ;
JONSSON, G .
JOURNAL OF NEUROCHEMISTRY, 1979, 32 (01) :129-132
[26]   PRIMARY STRUCTURE OF HUMAN INSULIN-LIKE GROWTH FACTOR-II [J].
RINDERKNECHT, E ;
HUMBEL, RE .
FEBS LETTERS, 1978, 89 (02) :283-286
[27]  
RINDERKNECHT E, 1978, J BIOL CHEM, V253, P2769
[28]   STRUCTURE OF THE RECEPTOR FOR INSULIN-LIKE GROWTH FACTOR-II - THE PUZZLE AMPLIFIED [J].
ROTH, RA .
SCIENCE, 1988, 239 (4845) :1269-1271
[29]   AUTOCRINE SECRETION AND MALIGNANT TRANSFORMATION OF CELLS [J].
SPORN, MB ;
TODARO, GJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1980, 303 (15) :878-880
[30]   TROPHIC EFFECTS OF INSULIN-LIKE GROWTH FACTOR-I ON FETAL-RAT HYPOTHALAMIC CELLS IN CULTURE [J].
TORRESALEMAN, I ;
NAFTOLIN, F ;
ROBBINS, RJ .
NEUROSCIENCE, 1990, 35 (03) :601-608