Novel dedifferentiated liposarcoma xenograft models reveal PTEN down-regulation as a malignant signature and response to PI3K pathway inhibition. Academic Article uri icon

Overview

abstract

  • Liposarcoma is a type of soft tissue sarcoma that exhibits poor survival and a high recurrence rate. Treatment is generally limited to surgery and radiation, which emphasizes the need for better understanding of this disease. Because very few in vivo and in vitro models can reproducibly recapitulate the human disease, we generated several xenograft models from surgically resected human dedifferentiated liposarcoma. All xenografts recapitulated morphological and gene expression characteristics of the patient tumors after continuous in vivo passages. Importantly, xenograftability was directly correlated with disease-specific survival of liposarcoma patients. Thus, the ability for the tumor of a patient to engraft may help identify those patients who will benefit from more aggressive treatment regimens. Gene expression analyses highlighted the association between xenograftability and a unique gene expression signature, including down-regulated PTEN tumor-suppressor gene expression and a progenitor-like phenotype. When treated with the PI3K/AKT/mTOR pathway inhibitor rapamycin alone or in combination with the multikinase inhibitor sorafenib, all xenografts responded with increased lipid content and a more differentiated gene expression profile. These human xenograft models may facilitate liposarcoma research and accelerate the generation of readily translatable preclinical data that could ultimately influence patient care.

publication date

  • February 12, 2013

Research

keywords

  • Down-Regulation
  • Liposarcoma
  • PTEN Phosphohydrolase
  • Phosphatidylinositol 3-Kinases
  • Signal Transduction
  • Xenograft Model Antitumor Assays

Identity

PubMed Central ID

  • PMC3620414

Scopus Document Identifier

  • 84875155842

Digital Object Identifier (DOI)

  • 10.1016/j.ajpath.2013.01.002

PubMed ID

  • 23416162

Additional Document Info

volume

  • 182

issue

  • 4