Research Papers:

Stat3-positive tumor cells contribute to vessels neoformation in primary central nervous system lymphoma

Simona Ruggieri, Roberto Tamma, Nicoletta Resta, Francesco Albano, Nicoletta Coccaro, Daria Loconte, Tiziana Annese, Mariella Errede, Giorgina Specchia, Rebecca Senetta, Paola Cassoni, Domenico Ribatti and Beatrice Nico _

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Oncotarget. 2017; 8:31254-31269. https://doi.org/10.18632/oncotarget.16115

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Simona Ruggieri1, Roberto Tamma1,5, Nicoletta Resta2, Francesco Albano3, Nicoletta Coccaro3, Daria Loconte2, Tiziana Annese1, Mariella Errede1, Giorgina Specchia3, Rebecca Senetta4, Paola Cassoni4, Domenico Ribatti1,5, Beatrice Nico1

1Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy

2Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari Medical School, Bari, Italy

3Department of Emergency and Transplantation, Section of Hematology, University of Bari Medical School, Bari, Italy

4Department of Biomedical Sciences and Human Oncology, University of Turin Medical School, Turin, Italy

5National Cancer Institute “Giovanni Paolo II”, Bari, Italy

Correspondence to:

Beatrice Nico, email: [email protected]

Domenico Ribatti, email: [email protected]

Keywords: angiogenesis, cancer stem cells, endothelium, lymphoma, Stat3

Received: January 12, 2017     Accepted: March 01, 2017     Published: March 10, 2017


With the aim of elucidating the relationship between Stat3 expression and tumor vessels abnormalities in the PCNLs, in this study we evaluated Stat3 and pStat3 expression by Real-time PCR and by immunohistochemistry in biopsy sections from PCNSL patients. Correlations of the expression levels with the presence of aberrant vessels were analyzed by confocal laser microscopy analysis, using FVIII as endothelial cell marker, CD133 and nestin as cancer stem cell (CSC) marker, CD20 as tumor cell marker, and Stat3. In addition, we investigated Stat3 mutations in lymphoma cells to clarify the role of the constitutive expression of Stat3 and of its phosphorylated forms. Results showed that in PCNSL, putative endothelial cells lining the vessels are heterogeneous, expressing FVIII/ pStat3/CD133 (presumably originally they are vascular progenitor cells), as well as FVIII/CD20/CD133 (presumably originally they are tumor cells). Finally, we detected a fraction of the FVIII+ endothelial cell that co-expressed Stat3 bearing a tetraploid karyotype, while no amplification signal for the Stat3 gene was detected.

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