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1.
Cancer Cell ; 24(1): 59-74, 2013 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-23845442

RESUMO

Sustained tumor progression has been attributed to a distinct population of tumor-propagating cells (TPCs). To identify TPCs relevant to lung cancer pathogenesis, we investigated functional heterogeneity in tumor cells isolated from Kras-driven mouse models of non-small-cell lung cancer (NSCLC). CD24(+)ITGB4(+)Notch(hi) cells are capable of propagating tumor growth in both a clonogenic and an orthotopic serial transplantation assay. While all four Notch receptors mark TPCs, Notch3 plays a nonredundant role in tumor cell propagation in two mouse models and in human NSCLC. The TPC population is enriched after chemotherapy, and the gene signature of mouse TPCs correlates with poor prognosis in human NSCLC. The role of Notch3 in tumor propagation may provide a therapeutic target for NSCLC.


Assuntos
Antígeno CD24/análise , Carcinoma Pulmonar de Células não Pequenas/etiologia , Integrina beta4/análise , Neoplasias Pulmonares/etiologia , Receptores Notch/fisiologia , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Receptor Notch3 , Esferoides Celulares
2.
J Proteome Res ; 11(2): 656-67, 2012 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-22106898

RESUMO

Gene expression profiling has defined molecular subtypes of breast cancer including those identified as luminal and basal. To determine if glycoproteins distinguish various subtypes of breast cancer, we obtained glycoprotein profiles from 14 breast cell lines. Unsupervised hierarchical cluster analysis demonstrated that the glycoprotein profiles obtained can serve as molecular signatures to classify subtypes of breast cancer, as well as to distinguish normal and benign breast cells from breast cancer cells. Statistical analyses were used to identify glycoproteins that are overexpressed in normal versus cancer breast cells, and those that are overexpressed in luminal versus basal breast cancer. Among the glycoproteins distinguishing normal breast cells from cancer cells are several proteins known to be involved in cell adhesion, including proteins previously identified as being altered in breast cancer. Basal breast cancer cell lines overexpressed a number of CD antigens, including several integrin subunits, relative to luminal breast cancer cell lines, whereas luminal breast cancer cells overexpressed carbonic anhydrase 12, clusterin, and cell adhesion molecule 1. The differential expression of glycoproteins in these breast cancer cell lines readily allows the classification of the lines into normal, benign, malignant, basal, and luminal groups.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Mama/química , Glicoproteínas/análise , Proteômica/métodos , Antígenos CD/biossíntese , Biomarcadores Tumorais/biossíntese , Mama/citologia , Mama/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Linhagem Celular , Linhagem Celular Tumoral , Análise por Conglomerados , Feminino , Citometria de Fluxo , Glicoproteínas/biossíntese , Humanos
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