The Tumor Microenvironment Controls Primary Effusion Lymphoma Growth in Vivo

@article{Staudt2004TheTM,
  title={The Tumor Microenvironment Controls Primary Effusion Lymphoma Growth in Vivo},
  author={Michelle R. Staudt and Yogita Kanan and Joseph H. Jeong and James F. Papin and Rebecca Hines-Boykin and Dirk P. Dittmer},
  journal={Cancer Research},
  year={2004},
  volume={64},
  pages={4790 - 4799}
}
Certain lymphomas in AIDS patients, such as primary effusion lymphoma (PEL), are closely associated with the lymphotropic γ herpes virus Kaposi’s sarcoma-associated herpes virus (KSHV), also called human herpesvirus 8. The virus is thought to be essential for tumorigenesis, yet systems to investigate PEL in vivo are rare. Here we describe PEL tumorigenesis in a new xenograft model. Embedded in Matrigel, PEL cells formed rapid, well-organized, and angiogenic tumors after s.c. implantation of C.B… 
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Productively Infected Murine Kaposi's Sarcoma-Like Tumors Define New Animal Models for Studying and Targeting KSHV Oncogenesis and Replication
TLDR
Two new murine models of Kaposi's sarcoma are described and it is proposed that these novel models are ideal for studying both viral and host contributions to KSHV-induced oncogenesis as well as for testing virally-targeted antitumor strategies for the treatment of KS.
Evidence for Multiple Subpopulations of Herpesvirus-Latently Infected Cells
TLDR
Single-cell RNA sequencing of latently infected PEL supports the existence of multiple subpopulations even within a single cell line and establishes a conceptual framework to design KSHV cure studies analogous to those for HIV.
Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma
TLDR
A direct xenograft model, UM-PEL-1, is developed by transferring freshly isolated human PEL cells into the peritoneal cavities of NOD/SCID mice without in vitro cell growth to show that bortezomib induces PEL remission and extends overall survival of mice bearing lymphomatous effusions.
lymphoma and Kaposi sarcoma Tumor suppressor microRNAs are underrepresented in primary effusion
TLDR
It is shown that the absence of miRNAs likewise can be used to determine tumor origin (miR155) and proliferation state, since tumor suppressor mi RNAs were significantly downregulated in primary effusion lymphoma and in Kaposi sarcoma, an endothelial cell tumor.
Reactivation of the p53 pathway as a treatment modality for KSHV-induced lymphomas.
TLDR
It is demonstrated that activation of the p53 pathway using murine double minute 2 (MDM2) inhibitor Nutlin-3a conveyed specific and highly potent activation of PEL cell killing, which presents new options for exploiting reactivation of p53 as what the authors believe to be a novel and highly selective treatment modality for this virally induced lymphoma.
Long-Term-Infected Telomerase-Immortalized Endothelial Cells: a Model for Kaposi's Sarcoma-Associated Herpesvirus Latency In Vitro and In Vivo
TLDR
KSHV-infected LTCs represent the first xenograft model for KS and should be of use to study KS pathogenesis and for the validation of anti-KS drug candidates.
Increased tumorigenicity of cells carrying recombinant human herpesvirus 8
TLDR
Whether cells carrying the HHV-8 BAC would form tumors when injected into mice was determined, enabling the use of this model to assess the influence of viral gene mutation on tumorigenesis.
The Zebrafish Xenograft Platform—A Novel Tool for Modeling KSHV-Associated Diseases
TLDR
The development of the first in vivo model for a virally induced lymphoma in zebrafish, whereby KSHV-infected PEL tumor cells engraft and proliferate in the yolk sac of zebra fish larvae, and it is found that PEL cell proliferation in xenografts was dependent on the host hypoxia-dependent translation initiation factor, eukaryotic initiation factor 4E2 (eIF4E2).
Kaposi sarcoma-associated herpesvirus and other viruses in human lymphomagenesis.
TLDR
The understanding of the mechanisms of viral lymphomagenesis should lead to the identification of novel therapeutic targets and to the development of rationally designed therapies.
Endothelial cell- and lymphocyte-based in vitro systems for understanding KSHV biology.
TLDR
This unifying model describes the current understanding of KS pathogenesis by drawing together multiple theories of KS progression that by themselves cannot account for the complexities of tumor development.
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