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Insulin-like growth factor I receptors and insulin-like growth factor-binding proteins in human parathyroid tumors

  • International Association of Endocrine Surgeons—Manuscripts Presented at the 35th World Congress of the International Society of Surgery, Hong Kong, August 1993
  • Published:
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Abstract

Studies have demonstrated the presence of epidermal growth factor receptors in human parathyroid tumors. However, there is little information on the effect of other peptide growth factors on parathyroid cell growth. We therefore studied the interaction of insulin-like growth factor I (IGF-I) with human parathyroid tumor cells. Parathyroid tissues were obtained from 24 patients with primary or secondary hyperparathyroidism. There were 15 solitary adenomas, 5 carcinomas, and 4 hyperplastic tissues. First, the binding of [125I]IGF-I to the crude membrane fractions was studied by competitive inhibition with unlabeled IGF-I. Second, isolated parathyroid cells were cultured with IGF-I and examined for DNA synthesis. The IGF-binding protein (IGFBP) content of tissue homogenates was determined by ligand blot analysis. The binding of [125I]IGF-I to parathyroid membranes was dependent on time, temperature, and pH of the medium. Maximum binding was obtained after incubation for 18 hours at 4°C. Specific binding to parathyroid cancer membranes (mean±SE, 10.75±10.55%/mg protein) was significantly (p<0.05) greater than that in adenoma tissues 3.71±2.11%/mg. The value in hyperplastic tissues (4.78±2.97%/mg) was not different from that in adenomas. Affinity cross-linking and autoradiography demonstrated the type I IGF receptors. Cultured parathyroid cells responded to IGF-I with increased DNA synthesis. The parathyroid tumor tissues expressed IGFBPs. These results suggest that IGF-I and IGFBPs are involved in the growth regulation of parathyroid tumor cells.

Résumé

Des études récentes ont démontré la présence de récepteurs de facteurs de croissance épidermiques dans les tumeurs parathyroïdes de l'homme. II existe cependant peu d'enseignement concernant l'effet des autres facteurs de crossance sur la cellule parathyroïde. Nous avons donc étudié l'interaction du facteur de croissance IGF-1 avec les cellules parathyroïdes de l'homme. Du tissu parathyroïde a été obtenu à partir de 24 patients ayant une hyperparathyroïdie primitive ou secondaire: 15 adénomes solitaires, 5 cancers et 4 parathyroïdes hyperplasiques. D'abord, on a étudié la liaison entre la GF-1[125] et des fractions de membrane brutes. On a ensuite mis en culture les cellules parathyroïdiennes isolées en présence d'IGF-1. Leur capacité de synthèse d'ADN a été mesurée. Le contenu en protéine de liaison (IGF-BP) dans les homogénéats de tissu a été déterminé par une analyse de “ligand blot”. La liaison de FIGF-1[125] aux membranes de la glande parathyroïde dépend du facteur temps, de la température et du pH. La liaison est maximale après une incubation de 18 h à 4°C. La liaison spécifique à la membrane de la parathyroïde cancéreuse (moyenne +/-ET [10.75 +/- 10.55]%/mg protéine) était significativement plus élevée (p<0.05) que pour les tissus d'adénome. (3.71+/-2.11). La valeur dans les tissus hyperplasiques (4.78 +/-2.97) n'étaient pas différente de celle des adénomes. Les récepteurs IGF ont pu être mis en évidence par le test d'affinité de “cross-link” et l'autoradiographie. La culture de cellules parathyroïdes ont répondu à l'IGF-1 par une augmentation de la synthèse d'ADN. On a trouvé que les IGF-BP sont fabriquées par les tissus parathyroïdes tumoraux. Ces résultats suggèrent que l'IGF-1 et l'IGFBP sont impliquées dans la régulation de la croissance des cellules parathyroïdes tumorales.

Resumen

Estudios recientes han demostrado la presencia de receptores del factor de crecimiento epidérmico en tumores paratiroideos humanos. Sin embargo, existe escasa información sobre los efectos de otros factores peptídicos de crecimiento sobre el crecimiento de la célula paratiroidea. Es por ello que procedimos a estudiar la interacción del factor de crecimiento-I similar a la insulina (IGF-I) en las células de tumores paratiroideas. Los tejidos paratiroideos fueron obtenidos de 24 pacientes con hiperparatiroidismo primario o secundario; hubo 15 adenomas solitarias, 5 carcinomas y 4 tejidos hiperplásicos. En primer lugar se estudió la ligación del péptido ligado con yodo radioactivo [125-1] IGF-I, a fracciones crudas de membrana mediante la inhibicón competitiva con IGF-I no marcado. En segundo lugar se cultivaron células paratiroideas aisladas con IGF-I que fueron analizadas para síntesis de ADN. El contenido de proteína ligadora de IGF-I (IGFBP) fue determinado mediante el método “ligand blot”. La ligación de [125-I]IGF-I a las membranas paratiroideas demostró ser dependiente del tiempo, la temperatura y el pH del medio. Se logró la máxima ligación luego de incubación por 18 h a 4°C. La ligación especifica a las membranas del cáncer paratiroideo (10.75 [±10.55]% por mg de proteina) fue significativamente (P<0.05) mayor (P<0.05) que la de los tejidos adenomatosos (3.71±2.11). El valor para el tejido hiperplásico (4.78±2.97) no fue differente del de los adenomas. La afinidad cruzada y la autorradiografía demostraron la presencia de receptores de IGF-I. Las células paratiroideas cultivadas respondieron al IGF-I con un incremento de la síntesis de ADN. Los tejidos tumorales paratiroideos expresaron IGFBPs. Los anteriores resultados sugieren que el IGF-I y las IGFBPs se hallan involucradas en la regulación del crecimiento de las células de tumores paratiroideas.

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Author notes

  1. Reiko Tanaka M.D.

    Present address: Department of Surgery, c/oDr. Edwin Kaplan, University of Chicago Medical Center, 5841 South Maryland Avenue, MC 5031, 60637, Chicago, IL, USA

Authors and Affiliations

  1. Department of Endocrine Surgery, Tokyo Women's Medical College, 8-1 Kawada-cho, Shinjuku, 162, Tokyo, Japan

    Reiko Tanaka M.D. & Takao Obara M.D.

  2. Department of Medicine, Tokyo Women's Medical College, 8-1 Kawada-cho, Shinjuku, 162, Tokyo, Japan

    Toshio Tsushima M.D.

  3. Institute for Growth Science, Tokyo, Japan

    Hitomi Murakami B.S. & Kazuo Shizume M.D.

Authors
  1. Reiko Tanaka M.D.
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  2. Toshio Tsushima M.D.
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  3. Hitomi Murakami B.S.
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  4. Kazuo Shizume M.D.
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  5. Takao Obara M.D.
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Tanaka, R., Tsushima, T., Murakami, H. et al. Insulin-like growth factor I receptors and insulin-like growth factor-binding proteins in human parathyroid tumors. World J. Surg. 18, 635–641 (1994). https://doi.org/10.1007/BF00353784

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