Cancer stem-like cells (CSCs) are a subpopulation of cancer cells responsible for tumor growth, and recent evidence suggests that CSCs also contribute to cancer metastasis. However, the heterogeneity of CSCs in metastasis capacities is still unclear in breast cancer. 

A team led by Dr. HU Guohong at Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences identified a subpopulation of breast cancer stem-like cells with lung metastasis capacity, and they revealed the role of these cells during cancer cell metastasis to lung. The study was published online in Cell Death & Disease.

Researchers showed that among the CD24^-/CD44⁺ breast CSCs, a subpopulation expressing the CD44 variant isoform CD44v had significantly higher lung metastasis capacity than cells expressing the standard isoform CD44s. These metastatic CSCs were also characterized by high expression of epithelial splicing regulatory protein 1 (ESRP1).

Further experiments showed that CD44v rather than CD44s in metastatic CSCs responded to osteopontin (OPN) in the lung environment to enhance cancer cell invasiveness and promote lung metastasis.

ESRP1 could promote CD44 pre-mRNA alternative splicing from CD44s to CD44v. In clinical samples, expression of ESRP1 and CD44v, rather than CD44s or total CD44, positively correlates with distant metastasis.

The findings revealed the heterogeneity of cancer stem-like cells in breast cancer, and suggested that CD44v and ESRP1 might be better prognosis markers and therapeutic targets for breast cancer metastasis.

This study was funded by grants from National Natural Science Foundation of China, Chinese Academy of Sciences and Science and Technology Commission of Shanghai Municipality.