Hematopoietic stem cells as a tool for the treatment of glioblastoma multiforme

Abstract

Glioblastoma multiforme is an aggressive malignant brain tumor with terminal consequences. A primary reason for its resistance to treatment is associated with cancer stem cells (CSCs), of which there are currently no effective ways to destroy. It remains unclear what cancer cells become a target of stem cell migration, what the role of this process is in oncogenesis and what stem cell lines should be used in developing antitumor technologies. Using modern post-genome technologies, the present study investigated the migration of human stem cells to cancer cells in vitro, the comparative study of cell proteomes of certain stem cells (including CSCs) was conducted and stem cell migration in vivo was examined. Of all glioblastoma cells, CSCs have the stability to attract normal stem cells. Critical differences in cell proteomes allow the consideration of hematopoietic stem cells (HSCs) as an instrument for interaction with glioblastoma CSCs. Following injection into the bloodstream of animals with glioblastoma, the majority of HSCs migrated to the tumor-containing brain hemisphere and penetrated the tumor tissue. HSCs therefore are of potential use in the development of methods to target CSCs.

Targeting Tumor Associated Macrophages to Overcome Conventional Treatment Resistance in Glioblastoma

“…Resident microglia are described to be involved in many processes including tumor growth and progression (Bryukhovetskiy et al, 2016;Matias et al, 2018). Microglia were shown to contribute to the invasiveness of GB by upregulating serpin family A member 3 (SERPINA3) expression in GB stem cells (GSCs), that is implicated in the remodeling of the extracellular matrix .…”

All-trans retinoic acid enhances temozolomide-induced autophagy in human glioma cells U251 via targeting Keap1/Nrf2/ARE signaling pathway

“…Median survival time of GBM patients is approximately 12–15 months after the first diagnosis ( 2 ). Conventional treatments for GBM patients are mostly surgical tumor excision followed by chemotherapy or radiation therapy ( 3 ). Although the therapies have increased the survival time to approximately 14.6 months, the advantages are unconspicuous ( 4 ).…”

Interaction of hematopoietic CD34+ CD45+ stem cells and cancer cells stimulated by TGF‑β1 in a model of glioblastoma in�vitro

“…Normal CD45 + CD34 + HSCs are able to migrate to cells of different types, although they have increased mobility towards cancer cells. In animals with implanted glial brain tumors, intravenously injected HSCs migrate to the tumor nidus and accumulate in areas of invasion and necrosis ( 32 ). A previous study reported that hematopoietic CD34 + CD45 + stem cells migrate towards glioblastoma cells and interact with them, indicative of a strong association between these cell types ( 32 ).…”

“…In animals with implanted glial brain tumors, intravenously injected HSCs migrate to the tumor nidus and accumulate in areas of invasion and necrosis ( 32 ). A previous study reported that hematopoietic CD34 + CD45 + stem cells migrate towards glioblastoma cells and interact with them, indicative of a strong association between these cell types ( 32 ). It is possible that by recruiting bone marrow cells, the tumor creates its own microenvironment, allowing it to optimize resources and escape the innate immune system and other defense mechanisms of the body ( 32 ).…”