Pathologic correlates of primary central nervous system lymphoma defined in an orthotopic xenograft model

Cigall Kadoch, Eduard B. Dinca, Ramona Voicu, Lingjing Chen, Diana Nguyen, Seema Parikh, Juliana Karrim, Marc A. Shuman, Clifford A. Lowell, Patrick A. Treseler, C. David James, James L. Rubenstein

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Purpose: The prospect for advances in the treatment of patients with primary central nervous system lymphoma (PCNSL) is likely dependent on the systematic evaluation of its pathobiology. Animal models of PCNSL are needed to facilitate the analysis of its molecular pathogenesis and for the efficient evaluation of novel therapeutics. Experimental Design: We characterized the molecular pathology of CNS lymphoma tumors generated by the intracerebral implantation of Raji B lymphoma cells in athymic mice. Lymphoma cells were modified for bioluminescence imaging to facilitate monitoring of tumor growth and response to therapy. In parallel, we identified molecular features of lymphoma xenograft histopathology that are evident in human PCNSL specimens. Results: Intracerebral Raji tumors were determined to faithfully reflect the molecular pathogenesis of PCNSL, including the predominant immunophenotypic state of differentiation of lymphoma cells and their reactive microenvironment. We show the expression of interleukin-4 by Raji and other B lymphoma cell lines in vitro and by Raji tumors in vivo and provide evidence for a role of this cytokine in the M2 polarization of lymphoma macrophages both in the murine model and in diagnostic specimens of human PCNSL. Conclusion: Intracerebral implantation of Raji cells results in a reproducible and invasive xenograft model, which recapitulates the histopathology and molecular features of PCNSL, and is suitable for preclinical testing of novel agents. We also show for the first time the feasibility and accuracy of tumor bioluminescence in the monitoring of a highly infiltrative brain tumor.

Original languageEnglish (US)
Pages (from-to)1989-1997
Number of pages9
JournalClinical Cancer Research
Volume15
Issue number6
DOIs
StatePublished - Mar 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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