A highly invasive subpopulation of MDA-MB-231 breast cancer cells shows accelerated growth, differential chemoresistance, features of apocrine tumors and reduced tumorigenicity in vivo.
The acquisition of an invasive phenotype is a prerequisite for metastasization, yet it is not clear whether or to which extent the invasive phenotype is linked to other features characteristic of metastatic cells. We selected an invasive subpopulation from the triple negative breast cancer cell line MDA-MB-231, performing repeated cycles of preparative assays of invasion through Matrigel covered membranes. The invasive sub-population of MDA-MB-231 cells exhibits stronger migratory capacity as compared to parental cells confirming the highly invasive potential of the selected cell line. Prolonged cultivation of these cells did not abolish the invasive phenotype. ArrayCGH, DNA index quantification and karyotype analyses confirmed a common genetic origin of the parental and invasive subpopulations and revealed discrete structural differences of the invasive subpopulation including increased ploidy and the absence of a characteristic amplification of chromosome 5p14.1-15.33. Gene expression analyses showed a drastically altered expression profile including features of apocrine breast cancers and of invasion related matrix-metalloproteases and cytokines. The invasive cells showed accelerated proliferation, increased apoptosis, and an altered pattern of chemo-sensitivity with lower IC50 values for drugs affecting the mitotic apparatus. However, the invasive cell population is significantly less tumorigenic in orthotopic mouse xenografts suggesting that the acquisition of the invasive capacity and the achievement of metastatic growth potential are distinct events.
Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Adriana
A
Amaro
Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Giovanna
G
Angelini
Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Valentina
V
Mirisola
Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Alessia Isabella
AI
Esposito
Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Daniele
D
Reverberi
Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Serena
S
Matis
Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Massimo
M
Maffei
Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Walter
W
Giaretti
Biotherapy, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Maurizio
M
Viale
Biotherapy, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Rosaria
R
Gangemi
Animal Facility, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Laura
L
Emionite
Immunology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Simonetta
S
Astigiano
Animal Facility, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Michele
M
Cilli
Institute of Laboratory Medicine, Ludwig-Maximilians-University, Munich, Germany.
Beatrice E
BE
Bachmeier
Institute of Laboratory Medicine, Ludwig-Maximilians-University, Munich, Germany.
Peter H
PH
Killian
Scientific and Technology Park, IRCCS MultiMedica, Milan, Italy.
Adriana
A
Albini
Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Ulrich
U
Pfeffer
D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis; D009336:Necrosis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype; D011003:Ploidies; D020641:Polymorphism, Single Nucleotide; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000473:pathology
aneuploidy; apocrine breast cancer; breast cancer; invasion; metastasis