Li Rong-Hui, Huang Wen-He, Wu Jun-Dong, Du Cai-Wen, Zhang Guo-Jun
The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China; Chang Jiang Scholar's Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
Oncol Lett. 2017 Feb;13(2):695-703. doi: 10.3892/ol.2016.5489. Epub 2016 Dec 12.
The purpose of the present study was to investigate the significance of C-X-C motif chemokine receptor type 4 (CXCR4) and epidermal growth factor receptors (EGFRs) in triple-negative breast cancer (TNBC). CXCR4 and EGFR expression levels were immunohistochemically determined in 207 primary breast cancer specimens. The associations between receptor expression and clinicopathological characteristics were analyzed, and receptor expression was also assessed as a prognostic factor. In the human MDA-MB-231 TNBC cell line, CXCR4 or EGFR was stably knocked down by short hairpin RNA, and the biological behavior of the cells, including migration, invasion and tumorigenesis, was investigated. The results revealed that TNBC was associated with younger age, higher histological grade and an aggressive phenotype. CXCR4 and EGFR were highly expressed in patients with TNBC, and those with high CXCR4 or EGFR expression exhibited an unfavorable prognosis in terms of disease-free survival and overall survival. In MDA-MB-231 cells, the expression of CXCR4 protein was decreased following EGFR silencing, while CXCR4 knockdown also caused a decrease in EGFR protein levels. The migratory and invasive capabilities of MDA-MB-231 cells were decreased following the knockdown of CXCR4 or EGFR expression. A strong correlation between CXCR4 and EGFR expression was identified in patients with TNBC. The results suggest that elevated expression levels of these two receptors may serve as predictive factors for poor prognosis in patients with TNBC. In addition, tumor proliferation, migration, invasion and tumorigenesis are weakened in MDA-MB-231 cells following suppression of CXCR4 or EGFR expression. Therefore, EGFR and CXCR4 may be potential therapeutic targets for TNBC.
本研究的目的是探讨C-X-C基序趋化因子受体4（CXCR4）和表皮生长因子受体（EGFRs）在三阴性乳腺癌（TNBC）中的意义。采用免疫组织化学方法测定了207例原发性乳腺癌标本中CXCR4和EGFR的表达水平。分析了受体表达与临床病理特征之间的相关性，并将受体表达作为预后因素进行评估。在人MDA-MB-231三阴性乳腺癌细胞系中，用短发夹RNA稳定敲低CXCR4或EGFR，研究细胞的生物学行为，包括迁移、侵袭和肿瘤发生。结果显示，三阴性乳腺癌与年轻、高组织学分级和侵袭性表型相关。CXCR4和EGFR在三阴性乳腺癌患者中高表达，CXCR4或EGFR高表达的患者在无病生存期和总生存期方面预后不良。在MDA-MB-231细胞中，EGFR沉默后CXCR4蛋白表达降低，而CXCR4敲低也导致EGFR蛋白水平降低。CXCR4或EGFR表达敲低后，MDA-MB-231细胞的迁移和侵袭能力降低。在三阴性乳腺癌患者中，CXCR4和EGFR表达之间存在强相关性。结果表明，这两种受体表达水平升高可能作为三阴性乳腺癌患者预后不良的预测因素。此外，抑制CXCR4或EGFR表达后，MDA-MB-231细胞的肿瘤增殖、迁移、侵袭和肿瘤发生减弱。因此，EGFR和CXCR4可能是三阴性乳腺癌的潜在治疗靶点。
