Molecular predictors of 3D morphogenesis by breast cancer cell lines in 3D culture.
Correlative analysis of molecular markers with phenotypic signatures is the simplest model for hypothesis generation. In this paper, a panel of 24 breast cell lines was grown in 3D culture, their morphology was imaged through phase contrast microscopy, and computational methods were developed to segment and represent each colony at multiple dimensions. Subsequently, subpopulations from these morphological responses were identified through consensus clustering to reveal three clusters of round, grape-like, and stellate phenotypes. In some cases, cell lines with particular pathobiological phenotypes clustered together (e.g., ERBB2 amplified cell lines sharing the same morphometric properties as the grape-like phenotype). Next, associations with molecular features were realized through (i) differential analysis within each morphological cluster, and (ii) regression analysis across the entire panel of cell lines. In both cases, the dominant genes that are predictive of the morphological signatures were identified. Specifically, PPARgamma has been associated with the invasive stellate morphological phenotype, which corresponds to triple-negative pathobiology. PPARgamma has been validated through two supporting biological assays.
Han
Ju
J
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
Chang
Hang
H
Giricz
Orsi
O
Lee
Genee Y
GY
Baehner
Frederick L
FL
Gray
Joe W
JW
Bissell
Mina J
MJ
Kenny
Paraic A
PA
Parvin
Bahram
B
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D006651:Histocytochemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008954:Models, Biological; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015203:Reproducibility of Results
D014408:Biomarkers, Tumor; D047495:PPAR gamma; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human