Abstract
BackgroundChemoresistance 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.MethodsImmunohistochemistry 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.ResultsThe protein level of S100P in breast cancer tissue was significantly higher than in benign fibroadenoma (p < 0.001). The S100P expression level was shown to be decreased by 46.55% after neoadjuvant chemotherapy (p = 0.015). Subgroup analysis revealed that S100P reduction (57.58%) was mainly observed in the HER2+ tumors (p = 0.027). Our in vitro 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.ConclusionS100P 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.
Highlights
Breast cancer is the most common malignancy and the second leading cause of cancer death in women [1]
The expression levels of S100 calcium-binding protein P (S100P) in 22 cases of breast cancer tissue samples before and after neoadjuvant chemotherapy, and 10 cases of breast fibroadenoma were detected by IHC
The results indicated that expression levels of S100P in breast cancer were higher than those in fibroadenoma (p < 0.001) (Figure 1A)
Summary
Breast cancer is the most common malignancy and the second leading cause of cancer death in women [1]. Chemotherapy is widely applied to improve the survival of patients with breast cancer. It has been a great challenge to tackle this problem for the better treatments of those breast cancer patients. This is the case for patients with triple-negative breast cancer (TNBC) type or metastasis because the response to chemotherapeutic drugs may be vital for them to survive [2]. 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. The role of S100P in chemoresistance in breast cancer has not been thoroughly determined
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