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KS-herpesvirus induces reprogramming of lymphatic endothelial cells to invasive mesenchymal cells
Date:12/14/2011

Human tumor viruses contribute to 15-20% of human cancers worldwide. Kaposi's sarcoma herpesvirus (KSHV) is an etiological agent for Kaposi's sarcoma (KS) and two other rare lymphoproliferative malignancies. KS is the most common cancer in HIV-infected untreated individuals and remains a primary cause of cancer deaths in many subequatorial African countries as a result of the AIDS pandemic. Researchers at the Institute of Biotechnology and Research Programs Unit (Genome-Scale Biology) at the University of Helsinki have discovered a novel viral oncogenesis mechanism in which KSHV oncogenes co-opt cellular signaling pathways and modify the cellular microenvironment more permissive for viral replication.

The findings by the group of Research Professor Pivi Ojala (Institute of Biotechnology, University of Helsinki) demonstrates the first lymphatic-specific endothelial-to-mesenchymal transition (EndMT) induced by a human tumor virus. The virus-induced EndMT can contribute to development of KS by giving rise to infected, invasive cells, and providing the virus a permissive cellular microenvironment for efficient spread of the virus.

"This information can be used for developing targeted therapies to prevent or at least slow down the progression of KS in immunosuppressed patients", Dr. Ojala says.

By developing a novel three-dimensional (3D) cell model to better mimic the in vivo microenvironment, the researchers show that KSHV induces transcriptional reprogramming of primary lymphatic endothelial cells (LEC) to mesenchymal cells via EndMT, a process implicated in promoting tumor growth and cell invasiveness. Mesenchymal markers were found co-distributed in the same cells with KSHV in primary KS tumor samples, suggesting that the 3D culture in this work succeeds in recapitulating the known heterogeneity of the cell types in KS tumors.

The results also reveal a key enzyme in cancer cell invasion, MT1-MMP, as a previously unrecognized
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Contact: Dr. Pivi Ojala
paivi.ojala@helsinki.fi
358-919-159-445
University of Helsinki
Source:Eurekalert

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