Altered chemokine receptor expression in papillary thyroid cancer.
BACKGROUND
Papillary thyroid cancer (PTC), the most prevalent type of differentiated thyroid carcinoma, displays a strikingly high frequency of lymph node metastasis (LNM). Recent data suggest that chemokines can play an important role in promoting tumor progression and metastatic migration of tumor cells. Here we have evaluated whether PTC tissues express a different pattern of chemokine receptors and if the expression of these receptors correlates with LNM.


METHODS
We assessed by immunohistochemistry and flow cytometry the expression of the chemokine receptors CCR3, CCR7, and CXCR4 in tumor and nonmalignant thyroid tissues from patients suffering from PTC. Expression of these receptors in PTC was correlated with the clinical pathological condition of PTC.


RESULTS
Our data show a significant enhancement of CCR3 (2.5 times higher, p = 0.038) and CXCR4 (1.7 times higher, p = 0.02) expression in PTC tissues as determined by immunohistochemical staining, and of CCR3 (3.5 times higher, p < 0.002) in the plasma membrane as determined by flow cytometric analyses, compared to controls. In addition, while CCR3 (100%) and CXCR4 (90%) were present in both tumor and control thyroid tissues, expression of CCR7 was scarcely detected in PTC cells (5-10%) and not found in control cells. CXCR4 expression correlated with the classical variant of PTC (p < 0.035) and extranodal extension (p < 0.010) in patients with LNM.


CONCLUSIONS
Our data support the notion that CCR3, CCR7, and CXCR4 are increasingly expressed in tumor cells from PTC and that CXCR4 expression in PTC could be a potential marker for enhanced tumor aggressiveness.
González
Hernán E
HE
Millennium Nucleus on Immunology and Immunotherapy, Department of Molecular Genetics, Faculty of Biological Sciences, The Pontifical Catholic University of Chile, Santiago, Chile.
Leiva
Andrea
A
Tobar
Hugo
H
Böhmwald
Karen
K
Tapia
Grace
G
Torres
Javiera
J
Mosso
Lorena M
LM
Bueno
Susan M
SM
Gonzalez
Pablo
P
Kalergis
Alexis M
AM
Riedel
Claudia A
CA
D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000378:metabolism*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D054397:Receptors, CCR3 / Q000096:biosynthesis; D054400:Receptors, CCR7 / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism*
C515350:CCR3 protein, human; C515370:CCR7 protein, human; D054397:Receptors, CCR3; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine