Molecular Definition of Breast Tumor Heterogeneity

Michail Shipitsin; Lauren L. Campbell; Pedram Argani; Stanislawa Weremowicz; Noga Bloushtain-Qimron; Jun Yao; Tatiana Nikolskaya; Tatiana Serebryiskaya; Rameen Beroukhim; Min Hu; Marc K. Halushka; Saraswati Sukumar; Leroy M. Parker; Karen S. Anderson; Lyndsay N. Harris; Judy E. Garber; Andrea L. Richardson; Stuart J. Schnitt; Yuri Nikolsky; Rebecca S. Gelman; Kornelia Polyak

doi:10.1016/j.ccr.2007.01.013

Molecular Definition of Breast Tumor Heterogeneity

Michail Shipitsin, Lauren L. Campbell, Pedram Argani, Stanislawa Weremowicz, Noga Bloushtain-Qimron, Jun Yao, Tatiana Nikolskaya, Tatiana Serebryiskaya, Rameen Beroukhim, Min Hu, Marc K. Halushka, Saraswati Sukumar, Leroy M. Parker, Karen S. Anderson, Lyndsay N. Harris, Judy E. Garber, Andrea L. Richardson, Stuart J. Schnitt, Yuri Nikolsky, Rebecca S. GelmanKornelia Polyak

Research output: Contribution to journal › Article › peer-review

1140 Scopus citations

Abstract

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-β 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.

Original language	English (US)
Pages (from-to)	259-273
Number of pages	15
Journal	Cancer cell
Volume	11
Issue number	3
DOIs	https://doi.org/10.1016/j.ccr.2007.01.013
State	Published - Mar 13 2007
Externally published	Yes

Keywords

CELLCYCLE

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2007.01.013

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Shipitsin, M., Campbell, L. L., Argani, P., Weremowicz, S., Bloushtain-Qimron, N., Yao, J., Nikolskaya, T., Serebryiskaya, T., Beroukhim, R., Hu, M., Halushka, M. K., Sukumar, S., Parker, L. M., Anderson, K. S., Harris, L. N., Garber, J. E., Richardson, A. L., Schnitt, S. J., Nikolsky, Y., ... Polyak, K. (2007). Molecular Definition of Breast Tumor Heterogeneity. Cancer cell, 11(3), 259-273. https://doi.org/10.1016/j.ccr.2007.01.013

Shipitsin, M, Campbell, LL, Argani, P, Weremowicz, S, Bloushtain-Qimron, N, Yao, J, Nikolskaya, T, Serebryiskaya, T, Beroukhim, R, Hu, M, Halushka, MK, Sukumar, S, Parker, LM, Anderson, KS, Harris, LN, Garber, JE, Richardson, AL, Schnitt, SJ, Nikolsky, Y, Gelman, RS & Polyak, K 2007, 'Molecular Definition of Breast Tumor Heterogeneity', Cancer cell, vol. 11, no. 3, pp. 259-273. https://doi.org/10.1016/j.ccr.2007.01.013

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title = "Molecular Definition of Breast Tumor Heterogeneity",

abstract = "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-β 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.",

keywords = "CELLCYCLE",

author = "Michail Shipitsin and Campbell, {Lauren L.} and Pedram Argani and Stanislawa Weremowicz and Noga Bloushtain-Qimron and Jun Yao and Tatiana Nikolskaya and Tatiana Serebryiskaya and Rameen Beroukhim and Min Hu and Halushka, {Marc K.} and Saraswati Sukumar and Parker, {Leroy M.} and Anderson, {Karen S.} and Harris, {Lyndsay N.} and Garber, {Judy E.} and Richardson, {Andrea L.} and Schnitt, {Stuart J.} and Yuri Nikolsky and Gelman, {Rebecca S.} and Kornelia Polyak",

note = "Funding Information: We greatly appreciate the help of Diana Calogrias and Dr. Myles Brown with the acquisition of human tissue samples and Natasha Pliss with immunohistochemical analyses. We thank Dr. Jonathan Yingling (Eli Lilly, Indianapolis, IN) for providing us with the TGFBR inhibitor; Drs. Ian Krop, Myles Brown, and Bert Vogelstein for their critical reading of the manuscript; and the Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada for SAGE library sequencing. This work was supported by Novartis Pharmaceuticals, Inc., NIH (CA89393 and CA94074) and DOD (DAMD17-02-1-0692 and W8IXWH-04-1-0452) grants awarded to K.P., and a DOD (BCO30054) grant awarded to S.S. and P.A. K.P. receives research support from and is a consultant to Novartis Pharmaceuticals, Inc. K.P. also receives research support from Biogen-Idec and is a consultant to Aveo Pharmaceuticals, Inc. ",

year = "2007",

month = mar,

day = "13",

doi = "10.1016/j.ccr.2007.01.013",

language = "English (US)",

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journal = "Cancer Cell",

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T1 - Molecular Definition of Breast Tumor Heterogeneity

AU - Shipitsin, Michail

AU - Campbell, Lauren L.

AU - Argani, Pedram

AU - Weremowicz, Stanislawa

AU - Bloushtain-Qimron, Noga

AU - Yao, Jun

AU - Nikolskaya, Tatiana

AU - Serebryiskaya, Tatiana

AU - Beroukhim, Rameen

AU - Hu, Min

AU - Halushka, Marc K.

AU - Sukumar, Saraswati

AU - Parker, Leroy M.

AU - Anderson, Karen S.

AU - Harris, Lyndsay N.

AU - Garber, Judy E.

AU - Richardson, Andrea L.

AU - Schnitt, Stuart J.

AU - Nikolsky, Yuri

AU - Gelman, Rebecca S.

AU - Polyak, Kornelia

N1 - Funding Information: We greatly appreciate the help of Diana Calogrias and Dr. Myles Brown with the acquisition of human tissue samples and Natasha Pliss with immunohistochemical analyses. We thank Dr. Jonathan Yingling (Eli Lilly, Indianapolis, IN) for providing us with the TGFBR inhibitor; Drs. Ian Krop, Myles Brown, and Bert Vogelstein for their critical reading of the manuscript; and the Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada for SAGE library sequencing. This work was supported by Novartis Pharmaceuticals, Inc., NIH (CA89393 and CA94074) and DOD (DAMD17-02-1-0692 and W8IXWH-04-1-0452) grants awarded to K.P., and a DOD (BCO30054) grant awarded to S.S. and P.A. K.P. receives research support from and is a consultant to Novartis Pharmaceuticals, Inc. K.P. also receives research support from Biogen-Idec and is a consultant to Aveo Pharmaceuticals, Inc.

PY - 2007/3/13

Y1 - 2007/3/13

N2 - 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-β 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.

AB - 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-β 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.

KW - CELLCYCLE

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U2 - 10.1016/j.ccr.2007.01.013

DO - 10.1016/j.ccr.2007.01.013

M3 - Article

C2 - 17349583

AN - SCOPUS:33847419142

SN - 1535-6108

VL - 11

SP - 259

EP - 273

JO - Cancer Cell

JF - Cancer Cell

IS - 3

ER -

Molecular Definition of Breast Tumor Heterogeneity

Abstract

Keywords

ASJC Scopus subject areas

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