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, from Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences identified a subpopulation of breast cancer stem-like cells with lung metastasis capacity, and revealed the role of these cells during cancer cell metastasis to lung.
Under the supervision of Dr. HU, Ph.D candidates HU Jing and LI Gang showed that among the CD24-/CD44+ breast CSCs, a subpopulation expressing the CD44 variant isoform CD44vhad 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). ESRP1 could promote CD44 pre-mRNA alternative splicing from CD44s to CD44v.
Further experiments showed that CD44v rather than CD44s in metastatic CSCsresponded to osteopontin (OPN) in the lung environment to enhance cancer cell invasiveness and promote lung metastasis.
In clinical samples, expression of ESRP1 and CD44v, rather than CD44s or total CD44, positively correlates with distant metastasis.
This work reveals the heterogeneity of cancer stem-like cells in breast cancer, and suggests that CD44v and ESRP1 might be better prognosis markers and therapeutic targets for breast cancer metastasis.
An article describing this work, entitled "A CD44v+ subpopulation of breast cancer stem-like cells with enhanced lung metastasis capacity" was published online in Cell Death & Disease on March 16th, 2017.
This study was funded by grants from National Natural Science Foundation of China (81430070, 31371409 and 81661148048), Chinese Academy of Sciences (QYZDB-SSW-SMC013, XDA12050101 and XDA01040402) and Science and Technology Commission of Shanghai Municipality (14431900800).
Dr. HU Guohong
Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science