CD74 expression and its therapeutic potential in thyroid carcinoma

Shih Ping Cheng, Chien Liang Liu, Ming Jen Chen, Ming Nan Chien, Ching Hsiang Leung, Chi Hsin Lin, Yi Chiung Hsu, Jie Jen Lee

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

CD74, the invariant chain of major histocompatibility complex class II, is also a receptor for macrophage migration inhibitory factor (MIF). CD74 and MIF have been associated with tumor progression and metastasis in hematologic and solid tumors. In this study, we found that 60 and 65% of papillary thyroid cancers were positive for CD74 and MIF immunohistochemical staining respectively. Anaplastic thyroid cancer was negative for MIF, but mostly positive for CD74 expression. Normal thyroid tissue and follicular adenomas were negative for CD74 expression. CD74 expression in papillary thyroid cancer was associated with larger tumor size (P=0.043), extrathyroidal invasion (P=0.021), advanced TNM stage (P=0.006), and higher MACIS score (P=0.026). No clinicopathological parameter was associated with MIF expression. Treatment with anti-CD74 antibody in thyroid cancer cells inhibited cell growth, colony formation, cell migration and invasion, and vascular endothelial growth factor secretion. In contrast, treatment with recombinant MIF induced an increase in cell invasion. Anti-CD74 treatment reduced AKT phosphorylation and stimulated AMPK activation. Our findings suggest that CD74 overexpression in thyroid cancer is associated with advanced tumor stage and may serve as a therapeutic target.

Original languageEnglish
Pages (from-to)179-190
Number of pages12
JournalEndocrine-Related Cancer
Volume22
Issue number2
DOIs
StatePublished - 1 Apr 2015

Keywords

  • Antibody
  • CD74
  • Macrophage migration inhibitory factor
  • Thyroid cancer

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