Pathways that govern normal stem cell (SC) function are often subverted in cancer. Here, we report the isolation to near purity of human normal mammary SC (hNMSCs), from cultured mammospheres, based on their ability to retain the lipophilic dye PKH26 as a consequence of their quiescent nature. We demonstrated that PKH26-positive cells possess all the characteristics of hNMSCs. The transcriptional profile of PKH26-positive cells (hNMSC signature) was able to predict biological and molecular features of breast cancers. By using markers of the hNMSC signature, we could prospectively isolate SCs from the normal gland and from breast tumors. Poorly-differentiated aggressive (G3) cancers displayed higher content of prospectively isolated cancer SCs, than well-differentiated less aggressive (G1) cancers. By comparing G3 and G1 tumors in xenotransplantation experiments, we directly demonstrated that G3s are enriched in cancer SCs. Our data support the notion that the heterogeneous phenotypical and molecular traits of human breast cancers are a function of their SC content.
Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content.
Specimen part
View SamplesJunction Adhesion Molecule-A (JAM-A) is present on leukocytes and platelets where it promotes cell adhesion and motility. We are interested in an interaction between JAM-A and tumor progression/metastases. To address this point, we mated JAM-A-/- mice and mouse mammary tumor model MMTV-PyMT mice which, which express polyoma middle T antigen under the control of mouse mammary tumor virus. MMTV-PyMT mice show 100% penetration of mammary tumor and highly metastases to lung. MMTV-PyMT mice without JAM-A show less primary tumor progression, therefore JAM-A enhance primary tumor progression. Then we are addressing the molecular mechanism of this phenomenon by in vivo. Furthermore, we would like to examine JAM-A deficient MMTV tumor signature.
Abrogation of junctional adhesion molecule-A expression induces cell apoptosis and reduces breast cancer progression.
Specimen part
View SamplesThe biological features of ovarian cancer stem cells (OCSC) remain elusive, mainly because 1) most studies so far have focused on cell lines that recapitulate the human disease only to a limited extend; and 2) because the identification of OCSC has relied on markers inferred from different and unrelated tumor types. Our study has harnessed the intrinsic, stemness-related properties of OCSC to identify and isolate this cell subpopulation from primary cultures freshly established from high-grade serous ovarian cancer (HGSOC), the most common and aggressive from of the disease. In addition, OCSC were compared to stem cell-enriched cultures from fallopian tube epithelium, which is the most accredited tissue of origin for HGSOC. The transcriptomes of the two cell types were compared to infer genes differentially regulated in OCSC.
CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop.
Cell line
View SamplesThe first bona fide PTP proto-oncogene was the Src-homology 2 domain-containing phosphatase SHP2 (encoded by PTPN11), an ubiquitously expressed PTP that transduces mitogenic, pro-survival, cell fate and/or pro-migratory signals from numerous growth factor-, cytokine- and extracellular matrix receptors. In malignancies, SHP2 is hyperactivated either downstream of oncoproteins or by mutations.We provide analysis of the breast cancer cells BT474 grown as xenografts in the presence or absence of SHP2 for 30 days.
Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop.
Cell line
View SamplesThe first bona fide PTP proto-oncogene was the Src-homology 2 domain-containing phosphatase SHP2 (encoded by PTPN11), an ubiquitously expressed PTP that transduces mitogenic, pro-survival, cell fate and/or pro-migratory signals from numerous growth factor-, cytokine- and extracellular matrix receptors. In malignancies, SHP2 is hyperactivated either downstream of oncoproteins or by mutations.We provide analysis of a primary triple-negative breast tumor grown as xenografts in the presence or absence of SHP2 for 30 days.
Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop.
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View SamplesThe first bona fide PTP proto-oncogene was the Src-homology 2 domain-containing phosphatase SHP2 (encoded by PTPN11), an ubiquitously expressed PTP that transduces mitogenic, pro-survival, cell fate and/or pro-migratory signals from numerous growth factor-, cytokine- and extracellular matrix receptors. In malignancies, SHP2 is hyperactivated either downstream of oncoproteins or by mutations.We provide analysis of the mammary epithelial cells MCF10A overexpressing human HER2 and HER3 and grown in 3D cultures for 15 days in the presence or absence of SHP2.
Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop.
Cell line
View SamplesIn an attempt to elucidate the molecular mechanisms underlying the multiple roles of L1 in endothelium, we checked whether manipulating its expression affected the transcriptome of lECs. To this purpose, we compared the gene expression profiles of L1-overexpressing and control lECs by Affymetrix, which revealed a remarkable effect of L1 overexpression on lECs transcriptome.
Endothelial deficiency of L1 reduces tumor angiogenesis and promotes vessel normalization.
Specimen part
View SamplesIn order to identify the effects of Tcfeb overexpression on the kidney transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the double heterozygous KSP_CRE/KSP_Tcfeb 14 days old mice as compared to control KSP_CRE mice
Modelling TFE renal cell carcinoma in mice reveals a critical role of WNT signaling.
Specimen part
View SamplesIn order to identify the effects of Tcfeb overexpression on the kidney transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the double heterozygous KSP_CRE/KSP_Tcfeb mice as compared to control KSP_CRE mice
Modelling TFE renal cell carcinoma in mice reveals a critical role of WNT signaling.
Specimen part
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