Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      In recent years, studies of cancer development and recurrence have been influenced by the cancer stem cells (CSCs)/cancer-initiating cells (CICs) hypothesis. According to this, cancer is sustained by highly positioned, chemoresistant cells with extensive capacity of self renewal, which are responsible for disease relapse after chemotherapy. Growth of cancer cells as three-dimensional non-adherent spheroids is regarded as a useful methodology to enrich for cells endowed with CSC-like features. We have recently reported that cell cultures derived from malignant pleural effusions (MPEs) of patients affected by adenocarcinoma of the lung are able to efficiently form spheroids in non-adherent conditions supplemented with growth factors. By expression profiling, we were able to identify a set of genes whose expression is significantly upregulated in lung tumor spheroids versus adherent cultures. One of the most strongly upregulated gene was stearoyl-CoA desaturase ( SCD1), the main enzyme responsible for the conversion of saturated into monounsaturated fatty acids. In the present study, we show both by RNA interference and through the use of a small molecule inhibitor that SCD1 is required for lung cancer spheroids propagation both in stable cell lines and in MPE-derived primary tumor cultures. Morphological examination and image analysis of the tumor spheroids formed in the presence of SCD1 inhibitors showed a different pattern of growth characterized by irregular cell aggregates. Electron microscopy revealed that the treated spheroids displayed several features of cellular damage and immunofluorescence analysis on optical serial sections showed apoptotic cells positive for the M30 marker, most of them positive also for the stemness marker ALDH1A1, thus suggesting that the SCD1 inhibitor is selectively killing cells with stem-like properties. Furthermore, SCD1-inhibited lung cancer cells were strongly impaired in their in vivo tumorigenicity and ALDH1A1 expression. These results suggest that SCD1 is a critical target in lung cancer tumor-initiating cells.

      Related collections

      Most cited references 39

      • Record: found
      • Abstract: found
      • Article: not found

      The epithelial-mesenchymal transition generates cells with properties of stem cells.

      The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: found

        Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis.

        There is a renewed interest in the ultimate role of fatty acid synthase (FASN)--a key lipogenic enzyme catalysing the terminal steps in the de novo biogenesis of fatty acids--in cancer pathogenesis. Tumour-associated FASN, by conferring growth and survival advantages rather than functioning as an anabolic energy-storage pathway, appears to necessarily accompany the natural history of most human cancers. A recent identification of cross-talk between FASN and well-established cancer-controlling networks begins to delineate the oncogenic nature of FASN-driven lipogenesis. FASN, a nearly-universal druggable target in many human carcinomas and their precursor lesions, offers new therapeutic opportunities for metabolically treating and preventing cancer.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          Identification and expansion of the tumorigenic lung cancer stem cell population.

          Lung carcinoma is often incurable and remains the leading cancer killer in both men and women. Recent evidence indicates that tumors contain a small population of cancer stem cells that are responsible for tumor maintenance and spreading. The identification of the tumorigenic population that sustains lung cancer may contribute significantly to the development of effective therapies. Here, we found that the tumorigenic cells in small cell and non-small cell lung cancer are a rare population of undifferentiated cells expressing CD133, an antigen present in the cell membrane of normal and cancer-primitive cells of the hematopoietic, neural, endothelial and epithelial lineages. Lung cancer CD133(+) cells were able to grow indefinitely as tumor spheres in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. The injection of 10(4) lung cancer CD133(+) cells in immunocompromised mice readily generated tumor xenografts phenotypically identical to the original tumor. Upon differentiation, lung cancer CD133(+) cells acquired the specific lineage markers, while loosing the tumorigenic potential together with CD133 expression. Thus, lung cancer contains a rare population of CD133(+) cancer stem-like cells able to self-renew and generates an unlimited progeny of non-tumorigenic cells. Molecular and functional characterization of such a tumorigenic population may provide valuable information to be exploited in the clinical setting.
            Bookmark

            Author and article information

            Affiliations
            [1 ]Department of Clinical and Molecular Medicine, Sapienza University of Rome , Italy
            [2 ]Laboratory of Research and Diagnostics, Department of Surgery ‘P.Valdoni', Sapienza University of Rome
            [3 ]Azienda Ospedaliera S. Andrea , Rome, Italy
            [4 ]Institute Pasteur-Fondazione Cenci Bolognetti , Italy
            [5 ]Department of Experimental and Clinical Medicine, University of Catanzaro ‘Magna Graecia' , Italy
            [6 ]Takis srl, Via di Castel Romano , Rome, Italy
            [7 ]Biogem s.c a r.l., Ariano Irpino (AV) , Italy
            [8 ]IRCCS Istituto Nazionale Tumori, Fondazione ‘G. Pascale' , Napoli, Italy
            Author notes
            [* ]Scientific Directorate, Istituto Nazionale Tumori, Via Mariano Semmola , Napoli 80131, Italy. Tel: +390815903756; Fax: +390815461688; E-mail: g.ciliberto@ 123456istitutotumori.na.it
            Journal
            Cell Death Dis
            Cell Death Dis
            Cell Death & Disease
            Nature Publishing Group
            2041-4889
            December 2013
            05 December 2013
            1 December 2013
            : 4
            : 12
            : e947
            24309934
            3877537
            cddis2013444
            10.1038/cddis.2013.444
            Copyright © 2013 Macmillan Publishers Limited

            This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

            Categories
            Original Article

            Cell biology

            cancer stem cells, scd1 inhibition, anoikis, lung cancer, tumor spheroids

            Comments

            Comment on this article