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Non-Hodgkin Lymphoma
CDCA7 is a critical mediator of lymphomagenesis that selectively regulates anchorage-independent growth
Ferrata Storti Foundation
Raúl Jiménez-P.,1 Carla Martín-Cortázar,1 Omar Kourani,1 Yuri Chiodo,1 Raul Cordoba,2,† María Purificación Domínguez-Franjo,3,‡
Juan Miguel Redondo,4,5 Teresa Iglesias6,7 and Miguel R. Campanero1,5
1Department of Cancer Biology, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM; 2Department of Hematology, University Hospital Infanta Sofía, San Sebastián de los Reyes; 3Department of Pathology, University Hospital Infanta Sofía, San Sebastián de los Reyes; 4Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, (CNIC); 5CIBERCV, Spain; 6Department of Endocrine and Nervous Systems Pathophysiology, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Madrid and 7Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
†Present address: Lymphoma Unit, Department of Hematology, Fundacion Jimenez Diaz University Hospital, Health Research Institute IIS-FJD, Madrid, Spain
Haematologica 2018 Volume 103(10):1669-1678
‡Present address: Department of Pathology, Hospital Rey Juan Carlos, Mostoles, Madrid, Spain
ABSTRACT
Tumor formation involves the acquisition of numerous capacities along the progression from a normal cell into a malignant cell, including limitless proliferation (immortalization) and anchorage- independent growth, a capacity that correlates extremely well with tumorigenesis. Great efforts have been made to uncover genes involved in tumor formation, but most genes identified participate in processes related to cell proliferation. Accordingly, therapies targeting these genes also affect the proliferation of normal cells. To identify potential targets for therapeutic intervention more specific to tumor cells, we looked for genes implicated in the acquisition of anchorage-independent growth and in vivo tumorigenesis capacity. A transcriptomic analysis identified CDCA7 as a candidate gene. Indeed, CDCA7 protein was upregulated in Burkitt’s lymphoma cell lines and human tumor biopsy specimens rela- tive to control cell lines and tissues, respectively. CDCA7 levels were also markedly elevated in numerous T and B-lymphoid tumor cell lines. While CDCA7 was not required for anchorage-dependent growth of normal fibroblasts or non-malignant lymphocytes, it was essential but not sufficient for anchorage-independent growth of lymphoid tumor cells and for lymphomagenesis. These data suggest that therapies aimed at inhibiting CDCA7 expression or function might significantly decrease the growth of lymphoid tumors.
Introduction
Most side effects of current therapies for cancer treatment are derived from their toxicity on actively proliferating normal cells, such as hematopoietic progenitors. These toxic effects likely occur because the targets for these therapies are also cru- cial for the proliferation of normal cells. The development of therapies more selec- tive for tumor cells might be facilitated by the identification of genes involved in properties specific of these cells.
Along the transformation of a normal cell into a highly malignant derivative, cells acquire numerous traits, including the ability to sustain chronic proliferation.1,2 Although immortalization is a fundamental trait of cancer cells, it is insufficient to promote malignant growth. NIH-3T3 fibroblasts, for instance, display replicative immortality but are not tumorigenic and display in vitro growth characteristics of
Correspondence:
mcampanero@iib.uam.es
Received: January 18, 2018. Accepted: June 4, 2018. Pre-published: June 7, 2018.
doi:10.3324/haematol.2018.188961
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/10/1669
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