The involvement of CXCR7 in modulating the progression of papillary thyroid carcinoma.

ABSTRACT

BACKGROUND: Although papillary thyroid carcinoma (PTC) has favorable prognosis, it is prone to cervical lymph node metastasis. Chemokine receptors play a role in metastasis of tumor cells, and accumulating evidence suggests an important role for the chemokine receptor CXCR7 in cancer development. We previously demonstrated high expression of CXCR7 protein in PTC tissue. In this study, we further evaluated the role of CXCR7 in PTC. METHODS: The expression of CXCR7 messenger RNA and protein in 79 cases of PTC and peritumoral tissues was detected by real-time quantitative polymerase chain reaction and Western blot. The association between CXCR7 expression and clinicopathologic characteristics in PTC was analyzed. Stable CXCR7 overexpression and knockdown PTC cells were constructed and used to examine proliferation, cell cycle, apoptosis and invasion of PTC cells by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, propidium iodide staining, 7-amino-actinomycin D staining, and invasion assay. We examined cell cycle regulatory protein levels by Western blot. RESULTS: CXCR7 messenger RNA and protein levels were markedly increased in PTC and correlated with tumor progression. CXCR7 could regulate proliferation, cell cycle, apoptosis, invasion, and the expression of cell cycle regulatory proteins involved in the S-G2 phase transition. Knockdown of CXCR7 in PTC cells suppressed cell proliferation and invasion, decreased expression of cyclin A, CDK2 and PCNA, increased expression of p21 and p57, induced S phase arrest, and promoted apoptosis. CONCLUSIONS: CXCR7 plays an important role in regulating growth and metastasis ability of PTC cell and provides a potential target for therapeutic interventions in PTC.