Relevance of breast cancer cell lines as models for breast tumours : an update



"Relevance of breast cancer cell lines as models for breast tumours : an update" by Marc Lacroix and
Guy Leclercq

The number of available breast cancer cell (BCC) lines is small, and only a very few of them have
been extensively studied. Whether they are representative of the tumours from which they originated
remains a matter of debate. Whether their diversity mirrors the well-known inter-tumoral
heterogeneity is another essential question. While numerous similarities have long been found
between cell lines and tumours, recent technical advances, including the use of micro-arrays and
comparative genetic analysis, have brought new data to the discussion. This paper presents most of
the BCC lines that have been described in some detail to date. It evaluates the accuracy of the few
of them widely used (MCF-7, T-47D, BT-474, SK-BR-3, MDA-MB-231, Hs578T) as tumour models. It is
concluded that BCC lines are likely to reflect, to a large extent, the features of cancer cells in
vivo. The importance of oestrogen receptor-alpha (gene ESR1) and Her-2/neu (ERBB2) as classifiers
for cell lines and tumours is underlined. The recourse to a larger set of cell lines is suggested
since the exact origin of some of the widely used lines remains ambiguous. Investigations on
additional lines is expected to improve our knowledge of BCC and of the dialogue that these maintain
with their surrounding normal cells in vivo.

Summary Introduction
1. Presentation of BCC lines - The question of representativeness
1.1) Multiplicity and variability of BCC lines
A) Distinctive features of BCC lines
B) BCC lines series "HCC (Hamon Cancer Centre) series" "SUM series" "HMT series" "21-series"
C) BCC lines variants
D) BCC lines from breast cancer patients with germ line mutations
E) The specificity of inflammatory breast cancer
1.2) The problem of BCC lines representativeness
2. Phenotype and invasiveness-based studies of BCC lines and tumours
2.1) Phenotype and invasiveness-based BCC line classification
A) Steroid receptor status and the bias in BCC line isolation
B) Distinct phenotypes - The "epithelial-mesenchymal transition" (EMT) hypothesis
C) Extended marker analysis
2.2) Analysis of breast tumours - Markers and grade - Comparison with cell lines
A) Molecular markers
B) Grade
2.3) Macroscopic homogeneity of breast tumours - Stable "portrait" during progression
A) Progression to invasiveness and markers/grade
B) Recurrence, metastasis
2.4) Concluding remarks on phenotype studies
3. Genetic studies on BCC lines and tumours
3.1) Karyotype and cytogenetic studies on BCC lines and tumours
3.2) Extension of genetic analyses: micro-array studies
A) BCC lines
B) Tumours
C) Comparison of genetic profiles of BCC lines and tumours
3.3) Epigenetic alterations - Hypermethylation
4. Dialogue between tumour cells and their cellular environment
5. Tumourigenicity of BCC lines in animal models Conclusion To which extent are individual tumours
genetically and phenotypically heterogeneous? Do BCC cultured in vitro maintain the
characteristics that they had in tumours? Do the panel of widely used BCC lines accurately
reflect the variety of tumour phenotypes?