Tumorigenic and metastatic activity of human thyroid cancer stem cells.
Thyroid carcinoma is the most common endocrine malignancy and the first cause of death among endocrine cancers. We show that the tumorigenic capacity in thyroid cancer is confined in a small subpopulation of stem-like cells with high aldehyde dehydrogenase (ALDH(high)) activity and unlimited replication potential. ALDH(high) cells can be expanded indefinitely in vitro as tumor spheres, which retain the tumorigenic potential upon delivery in immunocompromised mice. Orthotopic injection of minute numbers of thyroid cancer stem cells recapitulates the behavior of the parental tumor, including the aggressive metastatic features of undifferentiated thyroid carcinomas, which are sustained by constitutive activation of cMet and Akt in thyroid cancer stem cells. The identification of tumorigenic and metastagenic thyroid cancer cells may provide unprecedented preclinical tools for development and preclinical validation of novel targeted therapies.
Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy.
Matilde
M
Todaro
Flora
F
Iovino
Vincenzo
V
Eterno
Patrizia
P
Cammareri
Guido
G
Gambara
Virginia
V
Espina
Gaspare
G
Gulotta
Francesco
F
Dieli
Silvia
S
Giordano
Ruggero
R
De Maria
Giorgio
G
Stassi
D018263:Adenocarcinoma, Follicular / Q000201:enzymology / Q000473:pathology; D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002277:Carcinoma / Q000201:enzymology / Q000473:pathology; D002291:Carcinoma, Papillary / Q000201:enzymology / Q000473:pathology; D016022:Case-Control Studies; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000201:enzymology / Q000556:secondary*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000201:enzymology / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000473:pathology*; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
D012333:RNA, Messenger; D000444:Aldehyde Dehydrogenase; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt