Abstract

We investigated the expression status of periostin in breast cancer stem cells and its clinical implications in order to lay a foundation for managing breast cancer. CD44+/CD24−/line- tumor cells (CSC) from clinical specimens were sorted using flow cytometry. Periostin expression status was detected in CSC cells and 1,086 breast cancer specimens by Western blot and immunohistochemistry staining, with the CSC ratio determined by immunofluorescence double staining. The relationship between the periostin protein and clinico-pathological parameters and prognosis was subsequently determined. As a result, CSC cells are more likely to generate new tumors in mice and cell microspheres that are deficient in NOD/SCID compared to the control group. Periostin protein was expressed higher in CSC cells compared to the control cells and was found to be related to CSC chemotherapy resistance. Moreover, periostin expression was found to be related to the CSC ratio in 1,086 breast cancer specimens (P = 0.001). In total, 334 (30.76%) of the 1,086 breast cases showed high periostin expression. After universal and Spearman regression correlation analysis, periostin was observed to be related to histological grade, CSC ratio, lymph node metastasis, tumor size, and triple-negative breast cancer (all P<0.05). Furthermore, periostin was shown to attain a significantly more distant bone metastasis and worse disease-specific survival than those with none or low-expressed periostin protein (P = 0.001). In the Cox regression test, periostin protein was detected as an independent prognostic factor (P = 0.001). In conclusion, periostin was found to be related to the CSC and an independent prognostic factor for breast cancer. It is also perhaps a potential target to breast cancer.

Highlights

  • Breast cancer is the most common cause of death in female malignant tumor disease [1]

  • After 7 days of culture, single-cell suspensions of cancer stem cells (CSC) cells that were separated from the solid tumors produced viable mammospheres (20–100 mm), which could be passaged further

  • No mammosphere was produced by the non-CSC cells in the same culture condition

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Summary

Introduction

Breast cancer is the most common cause of death in female malignant tumor disease [1]. Surgical treatment is directed mainly at primary treatment, chemotherapy, radiotherapy, and endocrine therapy, whereas targeted treatment aims to eliminate the residual tumor cells and reduce the risk of recurrence and metastasis. Still relapse or metastasize after chemotherapy, radiotherapy, endocrine therapy, and targeted therapy. What causes the poor effects of chemotherapy? Why does targeted treatment have no effect on some patients? Stem cells, which represent only a very small percentage of the total tumor mass, have been found to be the source of some, and possibly most, cancers [4]. Breast cancer stem cells are a small group of tumor cells with the capacity to self-renew, a strong ability to form solid breast tumors, and the ability to differentiate into a relatively quiescent primitive group of cancer cells that are considered the underlying factor of tumor recurrence an the main reason breast cancers resist therapies [5]

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