Application of stem cell biology to breast cancer research has been limited by the lack of simple methods for identification and isolation of normal and malignant stem cells. Utilizing in vitro and in vivo experimental systems, we show that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties. These cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model. In breast carcinomas, high ALDH activity identifies the tumorigenic cell fraction, capable of self-renewal and of generating tumors that recapitulate the heterogeneity of the parental tumor. In a series of 577 breast carcinomas, expression of ALDH1 detected by immunostaining correlated with poor prognosis. These findings offer an important new tool for the study of normal and malignant breast stem cells and facilitate the clinical application of stem cell concepts.
Neutrophils, the most abundant type of leukocytes in blood, can form
neutrophil extracellular traps (NETs). These are pathogen-trapping structures
generated by expulsion of the neutrophil's DNA with associated
proteolytic enzymes. NETs produced by infection can promote cancer metastasis.
Here, we show that metastatic breast cancer cells can induce neutrophils to form
metastasis-supporting NETs in the absence of infection. Using intravital
imaging, we observed NET-like structures around metastatic 4T1 cancer cells that
had reached the lungs of mice. We also found NETs in clinical samples of
triple-negative human breast cancer. The formation of NETs stimulated the
invasion and migration of breast cancer cells in vitro. Inhibiting NET formation
or digesting NETs with DNase I blocked these processes. Treatment with
NET-digesting, DNase I-coated nanoparticles markedly reduced lung metastases in
mice. Our data suggest that induction of NETs by cancer cells is a previously
unidentified metastasis-promoting tumor-host interaction and a potential
therapeutic target.
This study confirms the prognostic significance of CTCs in patients with MBC receiving first-line chemotherapy. For patients with persistently increased CTCs after 21 days of first-line chemotherapy, early switching to an alternate cytotoxic therapy was not effective in prolonging OS. For this population, there is a need for more effective treatment than standard chemotherapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.