Abstract
Cancer is a major health problem that poses a great challenge to health care systems worldwide. Tools for cancer treatment have rapidly advanced in recent years, resulting in therapeutic strategies which are alternative and complementary to conventional treatment. To identify the cell surface receptors used by a tumor cell-adapted rotavirus and the cell death markers induced by its infection, we use Wt1-5, a rotavirus isolate recently adapted to tumor cells, to infect the human acute lymphoblastic leukemia cell line, Reh. The expression of cell surface receptors used by Wt1-5 was determined using flow cytometry and an antibody blocking assay to test for their implication in virus infection. Viral antigens and cell death markers induced by rotavirus infection were followed by flow cytometric analysis. The present study showed that rotavirus Wt1-5 was able to use cell surface proteins such as heat shock proteins (HSPs) 90, 70, 60 and 40, Hsc70, PDI and integrin β3. Rotavirus Wt1-5 induced cytotoxic effects including changes in cell membrane permeability, alteration of mitochondrial membrane potential, DNA fragmentation and activation of cell death signaling. Wt1-5 deserves to be further studied as a candidate oncolytic agent due to its ability to induce apoptosis in lymphoblastic leukemia-derived cells.
Highlights
Cancer is a major health problem that poses a great challenge to health care systems worldwide [1,2].The steady growth of the older adult population is resulting in a greater incidence of cancer rates [3].Acute lymphoblastic leukemia (ALL) has been defined as a malignant transformation and proliferation affecting lymphoid progenitor cells in the bone marrow, blood and extramedullary sites [4,5,6]
It has been shown that rotaviruses can be adapted to successfully infect tumor cells that express heat shock proteins (HSPs), protein disulfide isomerase (PDI) and integrin β3 on their outer cytoplasmic membrane [73]. Taking this previous background research into account, we investigated in the present work the potential utility of the tumor adapted rotavirus isolate Wt1-5 to infect, replicate and induce cell death in the human acute lymphoblastic leukemia cell line Reh
The percentage of rotavirus antigen-positive cells was found to be increased with the increasing MOI in Reh cells, while peripheral blood mononuclear cells (PBMCs) lacked viral antigens even at the highest MOIs used (Figure 1A)
Summary
The steady growth of the older adult population is resulting in a greater incidence of cancer rates [3]. Acute lymphoblastic leukemia (ALL) has been defined as a malignant transformation and proliferation affecting lymphoid progenitor cells in the bone marrow, blood and extramedullary sites [4,5,6]. In high-income countries, the overall long-term survival rates for children affected with ALL are higher than 80%, while in low-income countries, these survival rates are much lower [5,7]. The conventional treatment of ALL consists of staged chemotherapy divided into induction, consolidation and long-term maintenance phases [9]. Chemotherapy is of high toxicity and has significant adverse effects [9,10], besides the resistance of malignant cells to therapy [11]
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