CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases.
CEACAM1, also known as biliary glycoprotein (BGP), CD66a, pp120 and C-CAM1, is a member of the CEA immunoglobulin superfamily. CEACAM1 is a putative tumor suppressor based on diminished expression in some solid neoplasms such as colorectal carcinoma. However, CEACAM1 is overexpressed in some tumors such as non-small cell lung cancer. To clarify the mechanism of action of this cell adhesion molecule, we studied thyroid carcinoma that has a spectrum of morphologies and variable behavior allowing separation of proliferation from invasion and metastasis. CEACAM1 is expressed in thyroid carcinoma cell lines derived from tumors that exhibit aggressive behavior. Introduction of CEACAM1 into endogenously deficient WRO cells resulted in reduced cell cycle progression associated with p21 upregulation and diminished Rb phosphorylation. Forced CEACAM1 expression enhanced cell-matrix adhesion and migration and promoted tumor invasiveness. Conversely, small interfering RNA (siRNA)-mediated downregulation of CEACAM1 expression in MRO cells accelerated cell cycle progression and significantly enhanced tumor size in xenografted mice. CEACAM1 is not appreciably expressed in normal thyroid tissue or benign thyroid tumors. In a human thyroid tissue array, CEACAM1 reactivity was associated with metastatic spread but not with increased tumor size. These findings identify CEACAM1 as a unique mediator that restricts tumor growth whereas increasing metastatic potential. Our data highlight a complex repertoire of actions providing a putative mechanism underlying the spectrum of biologic behaviors associated with thyroid cancer.
Liu
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W
Department of Pathology, University Health Network and Toronto Medical Laboratories, and University Hospital Hamburg Eppendorf, Ontario, Canada.
Wei
W
W
Winer
D
D
Bamberger
A-M
AM
Bamberger
C
C
Wagener
C
C
Ezzat
S
S
Asa
S L
SL
D018263:Adenocarcinoma, Follicular / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*
D015703:Antigens, CD; C069847:CD66 antigens; C493956:CDKN1A protein, human; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D015815:Cell Adhesion Molecules; D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering; D050760:Cyclin-Dependent Kinase Inhibitor p27