Platelet-derived growth factor (PDGF)-PDGF receptor interaction activates bone marrow-derived mesenchymal stromal cells derived from chronic lymphocytic leukemia

Implications for an angiogenic switch

Wei D Ding, Traci R. Knox, Renee C. Tschumper, Wenting Wu, Susan M. Schwager, Justin C. Boysen, Diane F Jelinek, Neil Elliot Kay

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Malignant cells are capable of influencing the microenvironment in a manner that facilitates tumor cell survival. Bidirectional crosstalk between chronic lymphocytic leukemic (CLL) cells and marrowderived mesenchymal stromal cells (MSCs) activates both cell types. In this study, we observed that the conditioned medium (CM) obtained from CLL cells was able to induce Akt activation in MSC. Subsequent studies investigated the mechanism of MSC activation mediated by CLL-CM. Platelet-derived growth factor receptors (PDGFRs) were selectively activated in MSCs by CLL-CM and found to be critical receptors for CLL-CM-driven MSC proliferation and MSC Akt activation. The known ligands of PDGFR, platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), were detected in CLL-CM, but PDGF was the predominant ligand involved in the CM-mediated PDGFR activation. Both PDGF and VEGF were found to be elevated in the plasma of CLL patients with a positive association for high-risk factors and more advanced stage. Finally, we demonstrated that PDGF induced MSC VEGF production through a phosphatidylinositol 3-kinase (PI3K)-dependent mechanism. These results show that PDGF-PDGFR signaling influences at least the MSC in the microenvironment of CLL and may play a role in the induction of an angiogenic switch known to be permissive for disease progression.

Original languageEnglish (US)
Pages (from-to)2984-2993
Number of pages10
JournalBlood
Volume116
Issue number16
DOIs
StatePublished - Oct 21 2010

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Platelet-Derived Growth Factor Receptors
Platelet-Derived Growth Factor
B-Cell Chronic Lymphocytic Leukemia
Conditioned Culture Medium
Mesenchymal Stromal Cells
Bone
Bone Marrow
Switches
Chemical activation
Vascular Endothelial Growth Factor A
Phosphatidylinositol 3-Kinase
Ligands
Cell proliferation
Crosstalk
Cellular Microenvironment
Tumors
Cells
Association reactions
Plasmas
Disease Progression

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Platelet-derived growth factor (PDGF)-PDGF receptor interaction activates bone marrow-derived mesenchymal stromal cells derived from chronic lymphocytic leukemia : Implications for an angiogenic switch. / Ding, Wei D; Knox, Traci R.; Tschumper, Renee C.; Wu, Wenting; Schwager, Susan M.; Boysen, Justin C.; Jelinek, Diane F; Kay, Neil Elliot.

In: Blood, Vol. 116, No. 16, 21.10.2010, p. 2984-2993.

Research output: Contribution to journalArticle

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abstract = "Malignant cells are capable of influencing the microenvironment in a manner that facilitates tumor cell survival. Bidirectional crosstalk between chronic lymphocytic leukemic (CLL) cells and marrowderived mesenchymal stromal cells (MSCs) activates both cell types. In this study, we observed that the conditioned medium (CM) obtained from CLL cells was able to induce Akt activation in MSC. Subsequent studies investigated the mechanism of MSC activation mediated by CLL-CM. Platelet-derived growth factor receptors (PDGFRs) were selectively activated in MSCs by CLL-CM and found to be critical receptors for CLL-CM-driven MSC proliferation and MSC Akt activation. The known ligands of PDGFR, platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), were detected in CLL-CM, but PDGF was the predominant ligand involved in the CM-mediated PDGFR activation. Both PDGF and VEGF were found to be elevated in the plasma of CLL patients with a positive association for high-risk factors and more advanced stage. Finally, we demonstrated that PDGF induced MSC VEGF production through a phosphatidylinositol 3-kinase (PI3K)-dependent mechanism. These results show that PDGF-PDGFR signaling influences at least the MSC in the microenvironment of CLL and may play a role in the induction of an angiogenic switch known to be permissive for disease progression.",
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