title: CD74 expression and its therapeutic potential in thyroid carcinoma.
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.
authors.affiliation: Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan.
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Cheng
authors.affiliation: Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan.
authors.forename: Chien-Liang
authors.initials: CL
authors.lastname: Liu
authors.affiliation: Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan.
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Chen
authors.affiliation: Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan.
authors.forename: Ming-Nan
authors.initials: MN
authors.lastname: Chien
authors.affiliation: Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan.
authors.forename: Ching-Hsiang
authors.initials: CH
authors.lastname: Leung
authors.affiliation: Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan.
authors.forename: Chi-Hsin
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan.
authors.forename: Yi-Chiung
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan Department of SurgeryDivision of Endocrinology and MetabolismDepartment of Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, TaiwanMackay Junior College of MedicineNursing, and Management, No. 92, Sheng-Ching Road, Peitou, Taipei 11260, TaiwanDepartment of PharmacologyGraduate Institute of Medical Sciences, Taipei Medical University, Taipei, TaiwanDepartment of Medical ResearchMacKay Memorial Hospital, Taipei, TaiwanInstitute of Statistical ScienceAcademia Sinica, Taipei, Taiwan surg.mmh@gmail.com.
authors.forename: Jie-Jen
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome; D047368:Tumor Burden; D014945:Wound Healing
chemical_list: D000906:Antibodies; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; C045084:invariant chain; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: CD74; antibody; macrophage migration inhibitory factor; thyroid cancer