Molecular definition of breast tumor heterogeneity.
Cells with distinct phenotypes including stem-cell-like properties have been proposed to exist in normal human mammary epithelium and breast carcinomas, but their detailed molecular characteristics and clinical significance are unclear. We determined gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem-cell-like properties. CD24+ and CD44+ cells from individual tumors were clonally related but not always identical. CD44+ cell-specific genes included many known stem-cell markers and correlated with decreased patient survival. The TGF-beta pathway was specifically active in CD44+ cancer cells, where its inhibition induced a more epithelial phenotype. Our data suggest prognostic relevance of CD44+ cells and therapeutic targeting of distinct tumor cell populations.
Shipitsin
Michail
M
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Campbell
Lauren L
LL
Argani
Pedram
P
Weremowicz
Stanislawa
S
Bloushtain-Qimron
Noga
N
Yao
Jun
J
Nikolskaya
Tatiana
T
Serebryiskaya
Tatiana
T
Beroukhim
Rameen
R
Hu
Min
M
Halushka
Marc K
MK
Sukumar
Saraswati
S
Parker
Leroy M
LM
Anderson
Karen S
KS
Harris
Lyndsay N
LN
Garber
Judy E
JE
Richardson
Andrea L
AL
Schnitt
Stuart J
SJ
Nikolsky
Yuri
Y
Gelman
Rebecca S
RS
Polyak
Kornelia
K
D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051927:CD24 Antigen / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019070:Cell Lineage; D002478:Cells, Cultured; D000074283:Endothelial Protein C Receptor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D000074283:Endothelial Protein C Receptor; D018960:Hyaluronan Receptors; C478370:PROCR protein, human; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta