Cancer stem-like cells with increased expression of NY-ESO-1 initiate breast cancer metastasis

NY-ESO-1表达增加的癌干细胞样细胞启动乳腺癌转移

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作者:Mai-Ying Liu ,Hang Su ,Hua-Lan Huang ,Jing-Qi Chen

Abstract

Breast cancer stem-like cells (BCSLCs) with a CD44+/CD24-/low phenotype initiate the invasion and metastasis of breast cancer. The expression of New York oesophageal squamous cell carcinoma 1 (NY-ESO-1), one of the most immunogenic cancer-testicular antigens, is largely restricted to cancer and germ cells/placental trophoblasts, with little to no expression in normal adult somatic cells. Currently, few studies have reported the expression or function of NY-ESO-1 in BCSLCs. In the present study, immunohistochemistry indicated enhanced expression levels of NY-ESO-1/CD44 (P<0.01) and decreased expression levels of CD24 (P<0.01) in metastatic breast cancer tissues (MBCT) compared with non-MBCT. Additionally, the co-localization of CD44, CD24 and NY-ESO-1 in tissue samples was determined using immunofluorescence analysis. The results revealed that the expression of NY-ESO-1/CD44/CD24 was associated with breast cancer metastasis. Moreover, Spearman's rank correlation analysis indicated that CD44/CD24 expression was significantly correlated with that of NY-ESO-1. In the present study, mammosphere culture, a valuable method of BCSLC enrichment, was used to enrich MCF-7 and SK-BR-3 BCSLCs; immunofluorescence, western blotting and flow cytometry demonstrated increased expression levels of NY-ESO-1 and CD44, and low expression levels of CD24 in BCSLCs. Furthermore, the cell migration and invasion assays verified that BCSLCs with an increased NY-ESO-1 expression level exhibited greater invasive and migratory capacity compared with parental breast cancer cells. In addition to previously reported findings from the Oncomine database, it was ascertained that CD44+/CD24-/low BCSLCs with an increased level of NY-ESO-1 expression initiated the invasion and metastasis of breast cancer; therefore, NY-ESO-1 may serve as a novel target for metastatic breast cancer immunotherapy.

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