Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity

Jiyoung Kim, René Villadsen, Therese Sørlie, Louise Fogh, Signe Z Grønlund, Agla J Fridriksdottir, Irene Kuhn, Fritz Rank, Vera Timmermans-Wielenga, Hiroko Solvang, Paul A W Edwards, Anne-Lise Børresen-Dale, Lone Rønnov-Jessen, Mina J Bissell, Ole William Petersen

91 Citations (Scopus)

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.
Original languageEnglish
JournalNational Academy of Sciences. Proceedings
Volume109
Issue number16
Pages (from-to)6124-9
Number of pages6
ISSN0027-8424
DOIs
Publication statusPublished - 2012

Keywords

  • Animals
  • Breast Neoplasms
  • Cell Differentiation
  • Cell Line, Tumor
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin Receptor Common gamma Subunit
  • Mammary Neoplasms, Experimental
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, Nude
  • Mucin-1
  • N-Acetylglucosaminyltransferases
  • Naphthalenes
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells
  • Oligonucleotide Array Sequence Analysis
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Fingerprint

Dive into the research topics of 'Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity'. Together they form a unique fingerprint.

Cite this