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Mast cells have a protumorigenic role in human thyroid cancer

Oncogene volume 29, pages 6203–6215 (2010)Cite this article

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Abstract

In different human carcinoma types, mast cell infiltrate increases with respect to normal tissue and mast cell density correlates with a bad prognosis. To assess the role of mast cells in human thyroid cancer, we compared the density of tryptase-positive mast cells in 96 papillary thyroid carcinomas (PTCs) versus normal thyroid tissue from 14 healthy individuals. Mast cell density was higher in 95% of PTCs (n=91) than in control tissue. Mast cell infiltrate correlated with extrathyroidal extension (P=0.0005) of PTCs. We show that thyroid cancer cell-line-derived soluble factors induce mast cell activation and chemoattraction in vitro. Different mast cell lines (HMC-1 and LAD2) and primary human lung mast cells induced thyroid cancer cell invasive ability, survival and DNA synthesis in vitro. The latter effect was mainly mediated by three mast-cell-derived mediators: histamine, and chemokines CXCL1/GROα and CXCL10/IP10. We show that xenografts of thyroid carcinoma cells (8505-C) could recruit mast cells injected into the tail vein of mice. Co-injection of human mast cells accelerated the growth of thyroid cancer cell (8505-C) xenografts in athymic mice. This effect was mediated by increased tumor vascularization and proliferation, and was reverted by treating mice with sodium cromoglycate (Cromolyn), a specific mast cell inhibitor. In conclusion, our study data suggest that mast cells are recruited into thyroid carcinomas and promote proliferation, survival and invasive ability of cancer cells, thereby contributing to thyroid carcinoma growth and invasiveness.

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Acknowledgements

We would like to dedicate this paper to the memory of Professor Gaetano Salvatore, who continues to inspire our work. We are indebted to AS Kirshenbaum and JH Butterfield for the LAD2 and HMC-1 cell lines, respectively and to F Curcio for the P5 primary thyroid culture. We thank Mario Galgani and Salvatore De Simone for PBMC purification and 8505-C GFP-expressing cell sorting. We also thank Jean Ann Gilder for text editing. This study was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC), the Istituto Superiore di Oncologia (ISO), the Project ‘Applicazioni Biotecnologiche dalle molecole all'uomo’ (MoMa), the EC Contract 03695 (GenRisk-T), the Project ‘Sviluppo di nuovi farmaci capaci alterare il microambiente tumorale e ripristinare la risposta immune anti-tumorale’ (ACC) and the Project ‘Molecular diagnostic and prognostic markers of thyroid neoplasis’ RF-CAM-353005 of the Health Ministry. VG was a fellow of the Fondazione Italiana per la Ricerca sul Cancro (FIRC).

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Authors and Affiliations

  1. Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Naples, Italy

    R M Melillo, V Guarino, E Avilla, F Liotti & M Santoro

  2. Facoltà di Scienze Biotecnologiche, Naples, Italy

    R M Melillo

  3. Divisione di Immunologia Clinica ed Allergologia, Centro Interdipartimentale di Ricerca in Scienze Immunologiche di Base e Cliniche, Università di Napoli ‘Federico II’, Naples, Italy

    M R Galdiero, N Prevete, F W Rossi, A de Paulis & G Marone

  4. Dipartimento di Chirurgia, University of Pisa, Pisa, Italy

    F Basolo & C Ugolini

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  1. R M Melillo
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  2. V Guarino
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  3. E Avilla
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Correspondence to R M Melillo.

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Melillo, R., Guarino, V., Avilla, E. et al. Mast cells have a protumorigenic role in human thyroid cancer. Oncogene 29, 6203–6215 (2010). https://doi.org/10.1038/onc.2010.348

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