Navigation Links
KS-herpesvirus induces reprogramming of lymphatic endothelial cells to invasive mesenchymal cells

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 signaling molecule downstream of Notch to induce EndMT. Moreover, the 3D KSHV-LEC transcriptome showed significant up-regulation of invasion related genes, that were found co-regulated in 3D KSHV-LECs and KS biopsies and suggesting that virus-induced EndMT may contribute to development of KS. The results further demonstrate that the 3D culture provides a permissive microenvironment for continuous viral replication and persistence, indicating the importance of virus-cell interactions for viral spread and thereby for oncogenesis.

"The unraveled molecular mechanisms can lead to identification of novel cellular targets for pharmacological control in virus-associated cancers", Dr. Ojala says.

This work is a collaboration between the research teams headed by Kaisa Lehti, Kari Alitalo, Lauri Aaltonen, and Sampsa Hautaniemi (all from University of Helsinki), Chris Boshoff (UCL Cancer Institute, University College London) and Adam Grundhoff (Heinrich Pette Institute-Leibniz Institute for Experimental Virology). The project involves scientists from two Academy of Finland National Centre of Excellence Programs, the Translational Genome-Scale Biology and Cancer Biology.


Contact: Dr. Pivi Ojala
University of Helsinki

Related medicine news :

1. Single gene mutation induces endometrial cancer
2. CSHL scientists discover how a tumor suppressor induces senescence and staves off cancer
3. 2009 H1N1 vaccine safe and induces robust immune response in people with asthma
4. Novel immune system-based gene therapy induces strong responses in metastatic melanoma, sarcoma
5. Discovery of a new reprogramming mechanism for tumor cells
6. Reprogramming brain cells important first step for new Parkinsons therapy
7. Pitt researchers discover gene mutation linked to lymphatic dysfunction
8. New Study Uses Adult Stem Cells in Effort to Save Limbs of Patients with Peripheral Arterial Disease
9. New study suggests stem cells sabotage their own DNA to produce new tissues
10. Attacking cancer cells with hydrogel nanoparticles
11. UCR researcher identifies mechanism malaria parasite uses to spread in red blood cells
Post Your Comments:
(Date:11/28/2015)... ... ... Pixel Film Studios is back again with ProPanel: Pulse . With ... Users have full control over angle of view, speed method, start point, end point, ... get heads to turn. , ProPanel: Pulse offers fully customizable pulsating shape masks, all ...
(Date:11/27/2015)... ... November 27, 2015 , ... The rapid speed ... As people age, more care is needed, especially with Alzheimer’s, dementia and other ... are being overworked. The forgotten part of this equation: 80 percent of medical ...
(Date:11/27/2015)... ... November 27, 2015 , ... The ... of USA Today in Atlanta, Dallas, New York, Minneapolis, South Florida, with a ... component is distributed nationally, through a vast social media strategy and across a ...
(Date:11/27/2015)... ... November 27, 2015 , ... A simply groundbreaking television series, "Voices in America", ... delves into an array of issues that are presently affecting Americans. Dedicated to providing ... this show is changing the subjects consumers focus on, one episode at a time. ...
(Date:11/27/2015)... ... November 27, 2015 , ... Dr. Thomas Dunlap and Dr. ... Tucker Bierbaum with Emergency Medicine at St., Joseph Health System’s Santa Rosa Memorial ... conditions present in similar ways and require time-critical intervention to avoid large area heart ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... , November 26, 2015 ... Juntendo universitetssjukhus ser potential att använda ... magnetresonansbilder (MR-bilder) för patienter med multipel ... ett forskningsavtal med SyntheticMR AB för att ... forskningsprojekt på sjukhuset. Med SyMRI kan man ...
(Date:11/26/2015)... 26, 2015 ) ... Administration of High Viscosity Drugs" report to ... announced the addition of the "Self Administration ... offering. --> Research and Markets ( ... "Self Administration of High Viscosity Drugs" ...
(Date:11/25/2015)... Nov. 25, 2015 ... of the "Global Brain Monitoring Devices ... --> ) has announced ... Monitoring Devices Market 2015-2019" report to ... Markets ( ) has announced the ...
Breaking Medicine Technology: