TY  - EJOU
AU  - Haghshenas, Mohammad Reza 
AU  - Ashraf, Mohammad Javad 
AU  - Khademi, Bijan 
AU  - Ghaderi, Abbas 
AU  - Erfani, Nasrollah 
AU  - Razmkhah, Mahboobeh 

TI  - Chemokine and chemokine receptor patterns in patients with benign and malignant salivary gland tumors: a distinct role for CCR7
T2  - European Cytokine Network

PY  - 2017
VL  - 28
IS  - 1
SN  - 1952-4005

AB  - Background: To explore the molecular mechanisms involved in pathophysiology of malignant and
benign salivary gland tumors (SGTs), we investigated main tumor-inducing chemokines and chemokine receptors,
CXCL12/CXCR4/ACKR3 (CXCR7), CXCR3/CXCL10, CCR5/CCL5, CCL21/CCR7, CCL2, CCR4, CXCR5,
CCR6, and CXCL8 in tumor tissues. Patients and methods: Parotid tissues were obtained from 30 patients with
malignant and benign SGTs. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine
the mRNA expression pattern of the mentioned chemokines/chemokine receptors and immunohistochemistry
(IHC) was performed to verify the expression of CCR7. Results: Expression levels of CCR7 and CCR4 transcripts
were higher in the tumor tissues of malignant cases in comparison to benign ones (p = 0.03 and 0.02). Immunohistochemistry
analysis confirmed that the protein level of CCR7 concurred with the mRNA expression. CCL2
gene transcripts were observed with a higher expression in patients with tumor-free lymph nodes (LN<sup>–</sup>) and early
stages, whereas CCR7 transcript was higher in LN<sup>+</sup> and late stages of the disease. A significant inverse correlation
was found between CXCL10 transcript and tumor size in benign cases. The mRNA expression of CCR7, CCR4,
CXCR3, CCL21, CCL5, and CXCL12 was significantly higher in mucoepidermoid carcinoma in comparison to
pleomorphic adenoma subtypes (p < 0.05). Conclusion: On the basis of the present study, it was determined that
malignant and benign SGTs exhibit a distinct pattern of chemokines and chemokine receptors, which are probably
associated with known biological and clinical behaviors of these tumors. Significant increased CCR4 and CCR7
expression in malignant SGTs might play a central role in malignant transformation that introduces them as new
targets for cancer immunotherapy.
KW  - salivary gland tumors (SGTs)
KW  -  chemokine
KW  -  chemokine receptor

DO  - 10.1684/ecn.2017.0388