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Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity
- Source :
- Proceedings of the National Academy of Sciences of the United States of America. 109(16)
- Publication Year :
- 2012
-
Abstract
- The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells become basal-like to initiate tumors or to invade? Could luminally differentiated cells within a basally initiated hierarchy also be tumorigenic? To answer these questions, we used rare and mutually exclusive lineage markers to isolate subsets of luminal-like and basal-like cells from human breast tumors. We enriched for populations with or without prominent basal-like traits from individual tumors or single cell cloning from cell lines and recovered cells with a luminal-like phenotype. Tumor cells with basal-like traits mimicked phenotypic and functional behavior associated with stem cells assessed by gene expression, mammosphere formation and lineage markers. Luminal-like cells without basal-like traits, surprisingly, were fully capable of initiating invasive tumors in NOD SCID gamma (NSG) mice. In fact, these phenotypically pure luminal-like cells generated larger and more invasive tumors than their basal-like counterparts. The tumorigenicity and invasive potential of the luminal-like cancer cells relied strongly on the expression of the gene GCNT1 , which encodes a key glycosyltransferase controlling O-glycan branching. These findings demonstrate that basal-like cells, as defined currently, are not a requirement for breast tumor aggressiveness, and that within a single tumor there are multiple “stem-like” cells with tumorigenic potential casting some doubt on the hypothesis of hierarchical or differentiative loss of tumorigenicity.
- Subjects :
- Pathology
medicine.medical_specialty
Cellular differentiation
Transplantation, Heterologous
Mice, Nude
Breast Neoplasms
Biology
Naphthalenes
N-Acetylglucosaminyltransferases
03 medical and health sciences
Mice
0302 clinical medicine
Cancer stem cell
Mice, Inbred NOD
Cell Line, Tumor
medicine
Tumor Cells, Cultured
Animals
Humans
Neoplasm Invasiveness
Adapalene
030304 developmental biology
Oligonucleotide Array Sequence Analysis
Mice, Knockout
0303 health sciences
Mice, Inbred BALB C
Multidisciplinary
Reverse Transcriptase Polymerase Chain Reaction
Lineage markers
Gene Expression Profiling
Mucin-1
Mammary Neoplasms, Experimental
Cell Differentiation
Biological Sciences
Phenotype
Gene expression profiling
Gene Expression Regulation, Neoplastic
Cell culture
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Neoplastic Stem Cells
Female
RNA Interference
Stem cell
Interleukin Receptor Common gamma Subunit
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 109
- Issue :
- 16
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....6947f0575126a7ca12920e05ec92efe1