2 Tumor cell expression of VE-cadherin has been associated
with aggressive phenotype and poor prognosis in other tumor models, but has not been investigated in hematopoietic malignancies.3 Therefore, we investigated the regulation of VE-cadherin by BMSC and its contribution to Ph+ ALL therapeutic response. We determined that Ph+ ALL cell lines, as well as primary patient cells, express VE-cadherin. Exposure of Ph+ cells to Imatinib diminished VE-cadherin mRNA, which is blunted by Ph+ ALL contact with BMSC. Knockdown of VE-cadherin expression by siRNA rendered Ph + ALL cells more susceptible to chemotherapy, even in the presence of BMSC. Additionally, pre-treatment of Ph+ ALL
cells with ADH100191, a VE-cadherin antagonist, resulted in elevated Ser/Thr phosphorylation of beta-catenin see more and increased apoptosis selleck products during treatment. In contrast, lentiviral mediated expression of VE-cadherin in Ph- ALL cells resulted in increased resistance to treatment-induced apoptosis. These observations suggest a therapeutic role for VE-cadherin in modulation of chemoresistance in Ph+ ALL and demonstrate the importance of cues from the microenvironment in regulating tumor cell response to treatment. 1) Radich JP. Philadelphia chromosome-positive acute lymphocytic leukemia. Hematol Oncol Clin North Am 2001 Feb;15(1):21–36. 2) Wang L, O’Leary H, Fortney J, Gibson LF. Ph+/VE-cadherin+ identifies a stem cell like population of acute lymphoblastic leukemia sustained by bone marrow niche cells. find more Blood 2007 Nov 1;110(9):3334–44. 3) Hendrix MJ, et al. Expression and functional significance of VE-cadherin in aggressive human melanoma cells: role in vasculogenic mimicry. Proc Natl Acad Sci U S A 2001 Jul 3;98(14):8018–23. O100 Galectin-3 Binding Protein Produced Tau-protein kinase by Neuroblastoma Cells
Stimulates the Expression of Interleukin-6 in the Tumor Microenvironment Ayaka M. Silverman 1 , Yasushi Fukaya1, Leonid S. Metelitsa1, Robert C. Seeger1, Hiroyuki Shimada2, Ebrahim Zandi3, Yves A. DeClerck1 1 Department of Pediatrics, The Saban Research Institute of Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA, 2 Department of Pathology, The Saban Research Institute of Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA, 3 Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA There is recent evidence that mesenchymal cells derived from the bone marrow play an important role in bone metastasis in several cancers, including myeloma and neuroblastoma.