Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma.

The Journal of Experimental Medicine
Aarif Y KhakooToren Finkel

Abstract

Emerging evidence suggests that both human stem cells and mature stromal cells can play an important role in the development and growth of human malignancies. In contrast to these tumor-promoting properties, we observed that in an in vivo model of Kaposi's sarcoma (KS), intravenously (i.v.) injected human mesenchymal stem cells (MSCs) home to sites of tumorigenesis and potently inhibit tumor growth. We further show that human MSCs can inhibit the in vitro activation of the Akt protein kinase within some but not all tumor and primary cell lines. The inhibition of Akt activity requires the MSCs to make direct cell-cell contact and can be inhibited by a neutralizing antibody against E-cadherin. We further demonstrate that in vivo, Akt activation within KS cells is potently down-regulated in areas adjacent to MSC infiltration. Finally, the in vivo tumor-suppressive effects of MSCs correlates with their ability to inhibit target cell Akt activity, and KS tumors engineered to express a constitutively activated Akt construct are no longer sensitive to i.v. MSC administration. These results suggest that in contrast to other stem cells or normal stromal cells, MSCs possess intrinsic antineoplastic properties and that this stem cell popu...Continue Reading

References

Jan 1, 1976·Advances in Experimental Medicine and Biology·P M Gullino
Sep 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·B Mintz, K Illmensee
Feb 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·A C Braun, H N Wood
Apr 2, 1999·Science·M F PittengerD R Marshak
Sep 2, 1999·Journal of the National Cancer Institute·M S ReitzR C Gallo
Nov 2, 2001·Nature·T ReyaI L Weissman
Apr 12, 2002·The Journal of Biological Chemistry·Takashi MatsuiAnthony Rosenzweig
Jun 25, 2002·The Annals of Thoracic Surgery·Jay G ShakeBradley J Martin
Jan 23, 2003·The Annals of Thoracic Surgery·Abdulaziz Al-KhaldiKevin Lachapelle
Oct 11, 2003·Experimental Hematology·Katarina Le BlancOlle Ringdén
Nov 14, 2003·Cancer Cell International·Nives Pećina-Slaus
Dec 12, 2003·Nature Reviews. Cancer·Matthew Smalley, Alan Ashworth
Mar 30, 2004·Proceedings of the National Academy of Sciences of the United States of America·Akrit SodhiJ Silvio Gutkind
Apr 27, 2004·Oncogene·Nedime SerakinciMoustapha Kassem
May 6, 2004·Pediatric Transplantation·Sharon L Gardner
May 18, 2004·Experimental Hematology·Elisabeth H JavazonAlan W Flake
Jun 23, 2004·Critical Reviews in Oncology/hematology·Stewart Sell
Jun 30, 2004·Nature Immunology·David T Scadden
Jul 10, 2004·Circulation Research·Mark F Pittenger, Bradley J Martin
Jul 28, 2004·Cardiovascular Research·Vanessa P M van Empel, Leon J De Windt
Jul 31, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Noritoshi NagayaSoichiro Kitamura
Nov 4, 2004·Journal of the National Cancer Institute·Matus StudenyMichael Andreeff
Nov 19, 2004·Nature·Neil A BhowmickHarold L Moses
Nov 30, 2004·Science·Jeanmarie HoughtonTimothy C Wang
Dec 21, 2004·International Journal of Cancer. Journal International Du Cancer·Franz X BoschJürgen Kartenbeck
Mar 18, 2005·Cancer Science·Hirofumi HamadaYoshiro Niitsu
Apr 23, 2005·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Katarina Le Blanc, Olle Ringdén
Apr 23, 2005·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Hillard M LazarusAndrea Bacigalupo

❮ Previous
Next ❯

Citations

Apr 23, 2010·Cancer Metastasis Reviews·Scott A Bergfeld, Yves A DeClerck
Dec 21, 2010·Journal of Mammary Gland Biology and Neoplasia·Christelle P El-Haibi, Antoine E Karnoub
Aug 3, 2012·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Bo MaJun Ren
Aug 20, 2011·Molecular Pharmaceutics·Deepthi UppalapatiMasaaki Tamura
Sep 21, 2011·Cell Research·Rene RodriguezPablo Menendez
Mar 22, 2008·Gene Therapy·S KumarS Ponnazhagan
Nov 6, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Daniel BexellJohan Bengzon
Mar 26, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiancheng ChenXia Zhao
Oct 22, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ilaria T CavarrettaCestmir Altaner
Apr 22, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Daniel BexellJohan Bengzon
Nov 8, 2007·Nature Medicine·Douglas R Hurst, Danny R Welch
Jan 28, 2009·Nature Reviews. Immunology·Antonio UccelliVito Pistoia
Feb 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Seth B CoffeltAline B Scandurro
Dec 23, 2009·Cancer Biotherapy & Radiopharmaceuticals·Bing Feng, Longbang Chen
Jun 5, 2008·Stem Cells and Development·Ji Min YuJin Sup Jung
May 22, 2010·Stem Cells and Development·Federico MosnaMauro Krampera
Jul 31, 2010·Stem Cells and Development·Sabino CiavarellaFranco Silvestris
Aug 24, 2010·Tissue Engineering. Part B, Reviews·Vera S DonnenbergAlbert D Donnenberg
Oct 9, 2009·Tissue Engineering. Part C, Methods·Jessica E FrithPaul G Genever
May 22, 2010·Tissue Engineering. Part C, Methods·Massimo FaustiniMaria Luisa Torre
Jun 30, 2009·Rheumatology·Carine BouffiChristian Jorgensen
Aug 9, 2013·Plastic and Reconstructive Surgery·Jennifer S N VerhoekxSteven E R Hovius
May 14, 2009·Transplantation·Amelia BartholomewNorma Kenyon
Apr 15, 2010·Thorax·Michael R Loebinger, Sam M Janes
Jun 4, 2008·Cancer Research·Pravin J MishraDebabrata Banerjee
May 14, 2009·Cancer Research·Michael R LoebingerSam M Janes

❮ Previous
Next ❯

Methods Mentioned

BETA
fluorescence microscopy
FCS
flow cytometry
fluorescence-activated cell-sorting
transfection
protein assay

Software Mentioned

Prism
Imaris
FlowJo
ACT1
Excel
GraphPad
MetaMorph

Related Concepts

Related Feeds

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.