Environmental guidance of normal and tumor cell plasticity: epithelial mesenchymal transitions as a paradigm

Prindull, G.; Zipori, Dov

doi:10.1182/blood-2003-08-2807

Cited by 128 publications

(84 citation statements)

References 113 publications

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“…hFLMPCs appear to have mesendodermal origin, but further fate-map analysis and characterization of liver specification profiles will determine whether they arise from the cells described by Tremblay and Zaret (21) or are from a distinct progenitor niche. Mesenchymal-epithelial transitional cells are not uncommon in fetal development (25) and have been demonstrated in both rodent neonatal (26) and fetal livers (27), as well as human fetal livers, in which they have been reported to support hematopoiesis (28).…”

Section: Discussionmentioning

confidence: 99%

Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages

Dan¹,

Riehle

Lázaro³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

290

240

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Little is known about the differentiation capabilities of nonhematopoietic cells of the human fetal liver. We report the isolation and characterization of a human fetal liver multipotent progenitor cell (hFLMPC) population capable of differentiating into liver and mesenchymal cell lineages. Human fetal livers (74 -108 days of gestation) were dissociated and maintained in culture. We treated the colonies with geneticin and mechanically isolated hFLMPCs, which were kept in an undifferentiated state by culturing on feeder layers. We derived daughter colonies by serial dilution, verifying monoclonality using the Humara assay. hFLMPCs, which have been maintained in culture for up to 100 population doublings, have a high self-renewal capability with a doubling time of 46 h. The immunophenotype is: CD34؉, CD90؉, c-kit؉, EPCAM؉, c-met؉, SSEA-4؉, CK18؉, CK19؉, albumin؊, ␣-fetoprotein؊, CD44h؉, and vimentin؉. Passage 1 (P1) and P10 cells have identical morphology, immunophenotype, telomere length, and differentiation capacity. Placed in appropriate media, hFLMPCs differentiate into hepatocytes and bile duct cells, as well as into fat, bone, cartilage, and endothelial cells. Our results suggest that hFLMPCs are mesenchymal-epithelial transitional cells, probably derived from mesendoderm. hFLMPCs survive and differentiate into functional hepatocytes in vivo when transplanted into animal models of liver disease. hFLMPCs are a valuable tool for the study of human liver development, liver injury, and hepatic repopulation.epithelial-mesenchymal transition ͉ liver differentiation ͉ liver progenitor cell

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Section: Discussionmentioning

confidence: 99%

Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages

Dan¹,

Riehle

Lázaro³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

290

240

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“…17,18 EMT is a well-described process in morphogenesis, injured tissues and tumor progression, and it associates with dedif- …”

Section: Discussionmentioning

confidence: 99%

Frequent gene dosage alterations in stromal cells of epithelial ovarian carcinomas

Tuhkanen

Anttila

Kosma

et al. 2006

Intl Journal of Cancer

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Stromal cells are an active and integral part of epithelial neoplasms. We have previously observed allelic imbalance on chromosome 3p21 in both stromal and epithelial cells of ovarian tumors. This study was designed to explore gene dosage alterations throughout human chromosomes from stromal and epithelial cells of epithelial ovarian carcinomas. Thirteen stromal and 24 epithelial samples, microdissected from epithelial ovarian carcinomas, were analyzed using multiplex ligation-dependent probe amplification technique. Analysis covered 110 cancer related genes. Frequent genetic alterations were detected both in the stroma and epithelium of ovarian carcinomas. The mean number of altered genes per tumor was 10.8 in stroma and 23.6 in epithelium. In the stroma, the mean number of gains was 6.6 and of losses 4.2 and in the epithelium 13.7 and 9.9. The high number of changes associated with advanced tumor stage (p 5 0.035) and death due to ovarian cancer (p 5 0.032). The most frequent alteration was the deletion of the deleted in colorectal carcinoma (DCC) on chromosome 18q21.3 in 62% of samples. Loss of DCC was related to endometrioid subtype (p 5 0.033). Large chromosomal aberrations were detected on the basis of alterations in adjacent genes. Most importantly, 38 genes showed similar genetic alterations (gain-gain or loss-loss) in stromal and epithelial compartments of 11 tumor pairs. Thus, frequent genetic alterations in stromal cells of epithelial ovarian carcinomas resembled those of malignant epithelial cells and may indicate a common precursor cell type. Epithelial-mesenchymal transition may generate transformed cancer cells and modify the tumor microenvironment with distinct properties. ' 2006 Wiley-Liss, Inc.

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“…These are key components of adherence/tight junctions of cells. SNAIL also regulates the expression of genes controlling cell motility, proliferation and differentiation (Prindull & Zipori 2004, Klymkowsky & Savagner 2009. SNAIL also promotes epithelialmesenchymal transition and cell invasion (Oda et al 1994, Oku et al 2006.…”

Section: Introductionmentioning

confidence: 99%

High frequency of SNAIL-expressing cells confirms and predicts metastatic potential of phaeochromocytoma

Häyry¹,

Salmenkivi²,

Arola³

et al. 2009

Endocrine-Related Cancer

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Phaeochromocytomas are uncommon tumours of adrenal or extra-adrenal chromaffin tissue. About 2-26% of these have been reported to metastasize, but, on histological criteria, it is virtually impossible to predict malignant behaviour of the tumour. Using immunohistochemistry, we analysed the protein expression of SNAIL, a zinc-finger transcription factor, in a series of 50 phaeochromocytoma specimens from 42 patients. We found that SNAIL-expressing cells are frequent in metastatic primary tumours and their metastases, whereas in tumours without metastases, SNAIL expression is commonly absent. We conclude that the expression of SNAIL may be of use in predicting the metastatic potential of phaeochromocytoma.

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Environmental guidance of normal and tumor cell plasticity: epithelial mesenchymal transitions as a paradigm

Cited by 128 publications

References 113 publications

Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages

Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages

Frequent gene dosage alterations in stromal cells of epithelial ovarian carcinomas

High frequency of SNAIL-expressing cells confirms and predicts metastatic potential of phaeochromocytoma

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