Thyroid Cancer Resistance to Chemotherapeutic Drugs via Autocrine Production ofInterleukin-4 and Interleukin-10

Matilde Todaro, Diana Di Liberto, Ada Maria Florena, Monica Zerilli, Giorgio Stassi, Francesca Di Gaudio, Lucia Ricci-Vitiani, Ruggero De Maria, Giuseppe Di Gesu', Mariella Patti

Research output: Contribution to journalArticlepeer-review

110 Citations (Scopus)

Abstract

We investigated the mechanisms responsible for the widespread refractoriness to chemotherapeutic drugs observed in thyroid cancers. We show that malignant epithelial cells from papillary, follicular, and anaplastic thyroid carcinomas express high levels of Bcl-2 and Bcl-xL. Exogenous expression of either Bcl-2 or Bcl-xL in normal thyrocytes was sufficient to prevent chemotherapeutic drug-induced cytotoxicity. All of the histological thyroid cancer variants examined produced interleukin-4 (IL-4) and interleukin-10 (IL-10), which increased Bcl-2 and Bcl-xL levels and protected thyroid cells from chemotherapeutic agents. Exposure to neutralizing antibodies against IL-4 and IL-10 resulted in down-modulation of Bcl-2 and Bcl-xL, death of a considerable percentage of thyroid cancer cells, and sensitization of the residual tumor population to cytotoxic drug-induced apoptosis. In conclusion, autocrine production of IL-4 and IL-10 promotes thyroid tumor cell progression and resistance to chemotherapy through the up-regulation of antiapoptotic proteins. Thus, IL-4 and IL-10 may represent new therapeutic targets for the treatment of thyroid cancer.
Original languageEnglish
Pages (from-to)6784-6790
Number of pages7
JournalCancer Research
Volume63
Publication statusPublished - 2003

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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