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^–) and early stages, whereas CCR7 transcript was higher in LN⁺ 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.

中文翻译：

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涎腺和良性和恶性肿瘤患者的趋化因子和趋化因子受体模式：CCR7的独特作用。

背景

为了探讨与恶性和良性涎腺肿瘤（SGTs）病理生理有关的分子机制，我们研究了主要的肿瘤诱导趋化因子和趋化因子受体CXCL12 / CXCR4 / ACKR3（CXCR7），CXCR3 / CXCL10，CCR5 / CCL5，CCL21 / CCR ，肿瘤组织中的CCL2，CCR4，CXCR5，CCR6和CXCL8。

患者和方法

从30例恶性和良性SGT患者中获得腮腺组织。实时定量聚合酶链反应（qRT-PCR）用于确定上述趋化因子/趋化因子受体的mRNA表达模式，并进行免疫组化（IHC）验证CCR7的表达。

结果

与良性肿瘤相比，在恶性肿瘤的肿瘤组织中CCR7和CCR4转录本的表达水平更高（p = 0.03和0.02）。免疫组织化学分析证实CCR7的蛋白质水平与mRNA表达一致。在无肿瘤淋巴结（LN ^–）和早期患者中观察到CCL2基因转录物的表达较高，而在该疾病的LN ⁺和晚期患者中CCR7转录物的表达较高。在良性病例中，CXCL10转录本与肿瘤大小之间存在显着的负相关。与多形性腺瘤亚型相比，粘液表皮样癌中CCR7，CCR4，CXCR3，CCL21，CCL5和CXCL12的mRNA表达显着更高（p <0.05）。

结论

根据本研究，已确定恶性和良性SGT表现出不同的趋化因子和趋化因子受体模式，这可能与这些肿瘤的已知生物学和临床行为有关。恶性SGTs中CCR4和CCR7表达的显着增加可能在恶性转化中起着核心作用，从而将它们引入癌症免疫疗法的新靶标中。