Distinct populations of tumor-initiating cells derived from a tumor generated by rat mammary cancer stem cells

Authors/Editors

Dulbecco, Renato

Research Areas

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Publication Details

Output type: Journal article

Author list: Zucchi I., Astigiano S., Bertalot G., Sanzone S., Cocola C., Pelucchi P., Bertoli G., Stehling M., Barbieri O., Albertini A., Schöler H., Neel B., Reinbold R., Dulbecco R.

Publisher: National Academy of Sciences

Publication year: 2008

Journal: Proceedings of the National Academy of Sciences (0027-8424)

Volume number: 105

Issue number: 44

Start page: 16940

End page: 16945

Number of pages: 6

ISSN: 0027-8424

eISSN: 1091-6490

URL: http://api.elsevier.com/content/abstract/scopus_id:55949104447

Unpaywall Data

Open access status: green

Full text URL: https://europepmc.org/articles/pmc2575224?pdf=render

Abstract

Tumors derived from rat LA7 cancer stem cells (CSCs) contain a hierarchy of cells with different capacities to generate self-renewing spheres and tubules serially ex vivo and to evoke tumors in vivo. We isolated two morphologically distinct cell types with distinct tumorigenic potential from LA7-evoked tumors: cells with polygonal morphology that are characterized by expression of p21/ and p63 and display hallmarks of CSCs and elongated epithelial cells, which generate tumors with far less heterogeneity than LA7 CSCs. Serial transplantation of elongated epithelial cells results in progressive loss of tumorigenic potential; tumor heterogeneity; CD44, E-cadherin, and epithelial cytokeratin expression and increased α-smooth muscle actin I and vimentin expression. In contrast, serial transplantation of LA7 CSCs can be performed indefinitely and results in tumors that maintain their heterogeneity, consistent with self-renewal and multilineage differentiation potential. Collectively, our data show that polygonal cells are CSCs, whereas epithelial elongated cells are lineage-committed progenitors with tumorigenic potential, and suggest that tumor progenitors, although lacking indefinite self-renewal potential, nevertheless may make a substantial contribution to tumor development. Because LA7 cells can switch between conditions that favor maintenance of pure CSCs vs. differentiation into other tumor cell types, this cell system provides the opportunity to study factors that influence CSC self-renewal and differentiation. One factor, p63, was identified as a key gene regulating the transition between CSCs and early progenitor cells. © 2008 by The National Academy of Sciences of the USA.

Keywords

CD133, CD44, Mammospheres, p21/WAF1, Tumor-initiating progenitors

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