Early calcitonin hypersecretion and C cell hyperplasia in rats with high incidence of C cell tumors (Wag/Rij)

Khattab, Marwan; Pidoux, E.; Volle, G.E.; Bouizar, Zhor; Calmettes, C; Milhaud, G; Moukhtar, M.S.; Treilhou-Lahille, F.

doi:10.1016/0169-6009(89)90032-9

Cited by 11 publications

(9 citation statements)

References 14 publications

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“…1A, B. C cell diffuse hyperplasia is genetically determined in Wag/Rij rats and can be observed from the age of 3 months onwards [12]. With increasing age, (from 18 months onwards) more than half of the population develops a C cell tumour: during the early steps in oncogenesis, the proliferative C cells progressively invade the periphery of several adja-cent follicles, while the thyrocytes are drawn towards the centre (Fig.…”

Section: Resultsmentioning

confidence: 96%

“…An influence of altered interaction with ECM in C cell evolution towards MTC can be suggested, since between normal thyroid and large spontaneous MTCs a number of histological steps demonstrate obvious modifications in the relationships between ECM and C cells. All young animals exhibit progressive C cell hyperplasia [12]; that is, their perifollicular C cell foci increase in size, gradually surrounding the follicle beneath the BM completely. These cellular rearrangements in the pre-MTC state raise the problem of the origin of the BM around a C cell nodule in the absence of the follicular thyroid cells that would elaborate its constituents [1].…”

Section: Introductionmentioning

confidence: 99%

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Expression of laminin-2 by normal and neoplastic rat C cells during the development of medullary thyroid carcinoma

Lekmine

Feracci

Milhaud³

et al. 1999

Virchows Archiv

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Medullary thyroid carcinoma (MTC) originates from C cells, which secrete calcitonin (CT), their specific marker. C cells are located in contact with the basement membrane (BM) of the thyroid follicles, which is partly made up of the laminin-2 isoform synthesized by thyrocytes. During oncogenesis, proliferation of the C cells, invading the centre of the follicles, leads to a break in their normal contact with the BM. As specific interactions of cells with BM components, especially laminins, are important for proliferation and differentiation, we investigated the relationships of normal and neoplastic C cells with laminin in the Wag/Rij rat model of human MTC. Immunocytochemical studies showed a progressive loss of the laminin layer underlying the hyperplastic C cell nodules around the large dedifferentiated tumours. The alpha2, beta1 and gamma1 chains of the laminin-2 isoform were synthesized and secreted by rat MTC 6-23 cell cultures and the tumours induced by subcutaneous injection of these cells. In situ hybridization combined with anti-CT immunocytochemistry showed a low expression of alpha2 mRNA on differentiated C cells and thyrocytes, but an overexpression on immunonegative spontaneous MTC and induced intrathyroid tumours. The high level of alpha2 gene expression, together with tumour dedifferentiation, suggests a relationship with malignancy.

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Section: Resultsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Expression of laminin-2 by normal and neoplastic rat C cells during the development of medullary thyroid carcinoma

Lekmine

Feracci

Milhaud³

et al. 1999

Virchows Archiv

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“…The visualization of both immunoreactivities was performed using the peroxidase-antiperoxidase (PAP) procedure (23). The specificity of the reactions was tested using either normal serum or the specific antibodies saturated with an excess of the corresponding peptide in the first incubating medium.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Therefore, we decided to conduct similar studies on the murine model of human MTC, the old Wag/Rij rat (21). In this model, we have reported already the progression of the tumor and its CT secretory activity (22), as well as the biological status of the rats and of their thyroids during the pretumoral period (23)(24)(25).…”

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confidence: 97%

Evaluation of somatostatin biosynthesis, somatostatin receptors and tumor growth in murine medullary thyroid carcinoma

Ouazzani

Jc²,

Ge³

et al. 1994

European Journal of Endocrinology

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Spontaneous medullary thyroid carcinomas (MTCs) of old rat thyroids were analyzed for the expression of somatostatin and somatostatin binding sites in tumoral C cells in relation to the stage of tumor development, the mitotic activity of tumoral tissue and calcitonin biosynthesis as a marker of C cell differentiation. High levels of both immunoreactive somatostatin and its mRNA were detected in a subpopulation of tumoral C cells, gathered in areas suggesting a clonal proliferation and located preferentially at the periphery of the tumor. These cells also displayed high levels of calcitonin and its mRNA. However, many calcitonin immunoreactive cells showed no sign of somatostatin synthesis. The proliferative activity of the somatostatin-containing areas was low and slow compared to the areas lacking somatostatin production. However, it increased during the course of tumor growth. Somatostatin binding sites, measured with in vitro receptor autoradiography using 125I-[Tyr3]-octreotide or 125I-[Leu8, dTrp22, Tyr25]SS-28, were not detected in any of the MTCs tested. In rat MTC cells, somatostatin was associated with differentiation and slow proliferation, two parameters inversely correlated with the progression of malignancy. As expected, owing to the highly regulated secretion of the differentiated endocrine cell type, its presence was correlated with low basal calcitonin levels. However, the absence of somatostatin binding sites on any type of MTC cells does not favor a direct autocrine regulation of this peptide in this murine model of human MTC.

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“…For the response to i.v. calcium challenge, mice were injected with 100 l of CaCl 2 , containing 16 g of Ca 2ϩ ͞g body weight, and blood was collected 4 min after the beginning of the injection (31). Control data were obtained from nontransgenic mice of the same background, sex, and age as the transgenic mice tested.…”

Section: Methodsmentioning

confidence: 99%

Development of medullary thyroid carcinoma in transgenic mice expressing the RET protooncogene altered by a multiple endocrine neoplasia type 2A mutation

Michiels

Chappuis

Caillou

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

125

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Early calcitonin hypersecretion and C cell hyperplasia in rats with high incidence of C cell tumors (Wag/Rij)

Cited by 11 publications

References 14 publications

Expression of laminin-2 by normal and neoplastic rat C cells during the development of medullary thyroid carcinoma

Expression of laminin-2 by normal and neoplastic rat C cells during the development of medullary thyroid carcinoma

Evaluation of somatostatin biosynthesis, somatostatin receptors and tumor growth in murine medullary thyroid carcinoma

Development of medullary thyroid carcinoma in transgenic mice expressing the RET protooncogene altered by a multiple endocrine neoplasia type 2A mutation

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