Isolation and characterization of putative cancer stem cells in molecular subtypes of breast cancer
Principal investigator; Hegardt, Cecilia, Assistant Professor, PhD
Stem cells and cancer cells share several characteristics such as ability of self-renewal, multi-drug resistance and ability to survive under hypoxia. The concept that cancer arises from specific stem or progenitor cells draws increasing acceptance. Moreover, the existence of a distinct subpopulation of cancer stem cells within the bulk of tumor cells has been suggested, and may have important implications for drug resistance and metastatic ability. Breast cancer is a very heterogeneous disease and the molecular subtypes - known as luminal A and B, basal-like, HER2+ and normal breast-like - have been associated with diverse tumour characteristics and clinical outcome.
Isolation or enrichment of the putative cancer stem cell population can be accomplished by fluorescence activated cell sorting (FACS) based on the expression of cell surface proteins, e.g. CD44/CD24, CD133 or ALDH1, or by mammosphere culturing. Genomic, epigenetic and gene expression patterns from different cell populations can be studied using analysis of genome-wide mRNA and microRNA expression, copy number aberrations, SNP genotypes and CpG methylation. Important cancer stem cell properties such as self-renewal and tumour propagation are examined by in vivo and in vitro functional assays. The genetic and phenotypic characterization is then correlated to clinical data.
An increasing number of observations suggests the presence of rare cancer stem cells within a tumour, believed to be the main source of new cancer cells and more resistant to chemotherapy and irradiation than the rest of the tumour cells. If this is true, then there is an urgent need for detailed characterization of these cancer stem cells in order to device new treatment modalities. The large differences in survival between the different subtypes of breast tumours could reflect differences in cancer stem cell populations present within these subgroups, indicating the importance of isolating and characterizing the cancer stem cell population in different types of tumours.
5 recent original publications
Honeth Gabriella, Bendahl Pär-Ola, Ringnér Markus, Saal Lao, Gruvberger Sofia, Lövgren Kristina, Grabau Dorthe, Fernö Mårten, Borg Åke, Hegardt PhD Cecilia
The CD44(+)/CD24(-) phenotype is enriched in basal-like breast tumors
Breast Cancer Research. 2008; 10: R53 -
Olsson Eleonor, Honeth Gabriella, Bendahl Pär-Ola, Saal Lao, Gruvberger Sofia, Ringnér Markus, Vallon-Christersson Johan, Jönsson Göran B, Holm Karolina, Lövgren Kristina, Fernö Mårten, Grabau Dorthe, Borg Åke, Hegardt PhD Cecilia
CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers.
BMC cancer. 2011; 11: 418 -
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|Total financing:||0.6 MSEK||Gov grant for clinical research ("ALF"):||0.0 MSEK|
|Total external financing:||0.6 MSEK||Natl and intl prioritized grants:||0.0 MSEK|