Mast cells have a protumorigenic role in human thyroid cancer

R. M. Melillo, V. Guarino, E. Avilla, M. R. Galdiero, F. Liotti, N. Prevete, F. W. Rossi, F. Basolo, C. Ugolini, A. De Paulis, M. Santoro, G. Marone

Research output: Contribution to journalArticle

100 Citations (Scopus)

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 (n91) than in control tissue. Mast cell infiltrate correlated with extrathyroidal extension (P0.0005) 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.

Original languageEnglish
Pages (from-to)6203-6215
Number of pages13
JournalOncogene
Volume29
Issue number47
DOIs
Publication statusPublished - Nov 25 2010

Fingerprint

Thyroid Neoplasms
Mast Cells
Cromolyn Sodium
Heterografts
Chemokine CXCL1
Cell Count
Chemokine CXCL10
Tryptases
Cell Line
Survival
Growth
Nude Mice
Histamine
Tail
Veins
Neoplasms
Thyroid Gland
Carcinoma

Keywords

  • chemokine
  • mast cell
  • thyroid cancer

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Melillo, R. M., Guarino, V., Avilla, E., Galdiero, M. R., Liotti, F., Prevete, N., ... Marone, G. (2010). Mast cells have a protumorigenic role in human thyroid cancer. Oncogene, 29(47), 6203-6215. https://doi.org/10.1038/onc.2010.348

Mast cells have a protumorigenic role in human thyroid cancer. / Melillo, R. M.; Guarino, V.; Avilla, E.; Galdiero, M. R.; Liotti, F.; Prevete, N.; Rossi, F. W.; Basolo, F.; Ugolini, C.; De Paulis, A.; Santoro, M.; Marone, G.

In: Oncogene, Vol. 29, No. 47, 25.11.2010, p. 6203-6215.

Research output: Contribution to journalArticle

Melillo, RM, Guarino, V, Avilla, E, Galdiero, MR, Liotti, F, Prevete, N, Rossi, FW, Basolo, F, Ugolini, C, De Paulis, A, Santoro, M & Marone, G 2010, 'Mast cells have a protumorigenic role in human thyroid cancer', Oncogene, vol. 29, no. 47, pp. 6203-6215. https://doi.org/10.1038/onc.2010.348
Melillo RM, Guarino V, Avilla E, Galdiero MR, Liotti F, Prevete N et al. Mast cells have a protumorigenic role in human thyroid cancer. Oncogene. 2010 Nov 25;29(47):6203-6215. https://doi.org/10.1038/onc.2010.348
Melillo, R. M. ; Guarino, V. ; Avilla, E. ; Galdiero, M. R. ; Liotti, F. ; Prevete, N. ; Rossi, F. W. ; Basolo, F. ; Ugolini, C. ; De Paulis, A. ; Santoro, M. ; Marone, G. / Mast cells have a protumorigenic role in human thyroid cancer. In: Oncogene. 2010 ; Vol. 29, No. 47. pp. 6203-6215.
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