Cong Yizi, Cui Yuxin, Wang Suxia, Jiang Lei, Cao Jianqiao, Zhu Shiguang, Birkin Emily, Lane Jane, Ruge Fiona, Jiang Wen G, Qiao Guangdong
Department of Breast Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Front Oncol. 2020 Sep 15;10:566302. doi: 10.3389/fonc.2020.566302. eCollection 2020.
Chemoresistance remains one of the obstacles to overcome in the treatment of breast cancer. S100 calcium-binding protein P (S100P) has been observed to be overexpressed in several cancers and has been associated with drug resistance, metastasis, and prognosis. However, the role of S100P in chemoresistance in breast cancer has not been thoroughly determined.
Immunohistochemistry was used to evaluate the expression level of S100P protein in 22 pairs (pre-chemo and post-chemo) of breast cancer tissue from patients who underwent neoadjuvant chemotherapy. The influence of S100P on the biological behavior and chemosensitivity of breast cancer cells was then investigated.
The protein level of S100P in breast cancer tissue was significantly higher than in benign fibroadenoma ( < 0.001). The S100P expression level was shown to be decreased by 46.55% after neoadjuvant chemotherapy ( = 0.015). Subgroup analysis revealed that S100P reduction (57.58%) was mainly observed in the HER2+ tumors ( = 0.027). Our experiments showed that the knockdown of S100P suppressed the proliferation, adhesion, migrative and invasive abilities of T47D and SK-BR-3 breast cancer cells. We further demonstrated that this knockdown increased the chemoresistance to paclitaxel and cisplatin in SK-BR-3 cells. We found S100P exerted its function by upregulating NF-κB, CCND1 and Vimentin, but downregulating E-cadherin.
S100P promotes the aggressive properties of breast cancer cells and may be considered as a promising therapeutic target. Moreover, S100P can be used to predict the therapeutic effect of chemotherapy in HER2+ breast cancer patients.
化疗耐药仍然是乳腺癌治疗中需要克服的障碍之一。已观察到S100钙结合蛋白P（S100P）在多种癌症中过度表达，并与耐药性、转移和预后相关。然而，S100P在乳腺癌化疗耐药中的作用尚未完全明确。
采用免疫组织化学法评估22对（化疗前和化疗后）接受新辅助化疗患者的乳腺癌组织中S100P蛋白的表达水平。随后研究S100P对乳腺癌细胞生物学行为和化疗敏感性的影响。
乳腺癌组织中S100P的蛋白水平显著高于良性纤维腺瘤（<0.001）。新辅助化疗后S100P表达水平下降了46.55%（=0.015）。亚组分析显示，S100P降低（57.58%）主要见于HER2+肿瘤（=0.027）。我们的实验表明，敲低S100P可抑制T47D和SK-BR-3乳腺癌细胞的增殖、黏附、迁移和侵袭能力。我们进一步证明，这种敲低增加了SK-BR-3细胞对紫杉醇和顺铂的化疗耐药性。我们发现S100P通过上调NF-κB、CCND1和波形蛋白，但下调E-钙黏蛋白发挥其功能。
S100P促进乳腺癌细胞的侵袭性，可能是一个有前景的治疗靶点。此外，S100P可用于预测HER2+乳腺癌患者的化疗疗效。
