Pleiotrophin produced by multiple myeloma induces transdifferentiation of monocytes into vascular endothelial cells: A novel mechanism of tumor-induced vasculogenesis

Haiming Chen, Richard A. Campbell, Yunchao Chang, Mingjie Li, Cathy S. Wang, Jennifer Li, Eric Sanchez, Michael Share, Jeffrey Steinberg, Ariana Berenson, Dror Shalitin, Zhaohui Zeng, Dorina Gui, Pablo Perez-Pinera, Ronald J. Berenson, Jonathan Said, Benjamin Bonavida, Thomas F. Deuel, James R. Berenson

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Enhanced angiogenesis is a hallmark of cancer. Pleiotrophin (PTN) is an angiogenic factor that is produced by many different human cancers and stimulates tumor blood vessel formation when it is expressed in malignant cancer cells. Recent studies show that monocytes may give rise to vascular endothelium. In these studies, we show that PTN combined with macrophage colony-stimulating factor (M-CSF) induces expression of vascular endothelial cell (VEC) genes and proteins in human monocyte cell lines and monocytes from human peripheral blood (PB). Monocytes induce VEC gene expression and develop tube-like structures when they are exposed to serum or cultured with bone marrow (BM) from patients with multiple myeloma (MM) that express PTN, effects specifically blocked with antiPTN antibodies. When coinjected with human MM cells into severe combined immunodeficient (SCID) mice, green fluorescent protein (GFP)-marked human monocytes were found incorporated into tumor blood vessels and expressed human VEC protein markers and genes that were blocked by anti-PTN antibody. Our results suggest that vasculogenesis in human MM may develop from tumoral production of PTN, which orchestrates the transdifferentiation of monocytes into VECs.

Original languageEnglish (US)
Pages (from-to)1992-2002
Number of pages11
JournalBlood
Volume113
Issue number9
DOIs
StatePublished - Feb 26 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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