Treating Metastatic Brain Cancers With Stem Cells

Abstract

Stem cell therapy may present an effective treatment for metastatic brain cancer and glioblastoma. Here we posit the critical role of a leaky blood-brain barrier (BBB) as a key element for the development of brain metastases, specifically melanoma. By reviewing the immunological and inflammatory responses associated with BBB damage secondary to tumoral activity, we identify the involvement of this pathological process in the growth and formation of metastatic brain cancers. Likewise, we evaluate the hypothesis of regenerating impaired endothelial cells of the BBB and alleviating the damaged neurovascular unit to attenuate brain metastasis, using the endothelial progenitor cell (EPC) phenotype of bone marrow-derived mesenchymal stem cells. Specifically, there is a need to evaluate the efficacy for stem cell therapy to repair disruptions in the BBB and reduce inflammation in the brain, thereby causing attenuation of metastatic brain cancers. To establish the viability of stem cell therapy for the prevention and treatment of metastatic brain tumors, it is crucial to demonstrate BBB repair through augmentation of vasculogenesis and angiogenesis. BBB disruption is strongly linked to metastatic melanoma, worsens neuroinflammation during metastasis, and negatively influences the prognosis of metastatic brain cancer. Using stem cell therapy to interrupt inflammation secondary to this leaky BBB represents a paradigm-shifting approach for brain cancer treatment. In this review article, we critically assess the advantages and disadvantages of using stem cell therapy for brain metastases and glioblastoma.

Mechanism of RIP2 enhancing stemness of glioma cells induces temozolomide resistance

“…The NF‐κB signaling pathway is, however, also involved in maintaining cancer cell stemness. For example, NF‐κB maintains the stemness of colon cancer cells by down‐regulating miR‐195‐5p/497‐5p and up‐regulating MCM2 37 . To investigate whether NF‐κB is involved in mediating RIP2‐induced stemness of U251 cells, we observed the intervention effect of the NF‐κB chemical inhibitor SC75741.…”

“…A retrospective analysis of many studies found that stem cell therapy may present an effective treatment for metastatic brain cancer and glioblastoma 37 . Therefore, eliminating glioma cell stemness is one of the critical strategies for clinical treatment.…”

“…For example, NF-κB maintains the stemness of colon cancer cells by down-regulating miR-195-5p/497-5p and up-regulating MCM2. 37 To investigate whether NF-κB is involved in mediating RIP2-induced stemness of U251 cells, we observed the intervention effect of the NF-κB chemical inhibitor SC75741. In both in vitro and in vivo studies, SC75741 treatment inhibited RIP2-induced upregulation of In cell and xenograft studies, we found that SC75741 treatment inhibited TMZ resistance induced by RIP2 overexpression.…”

“…A retrospective analysis of many studies found that stem cell therapy may present an effective treatment for metastatic brain cancer and glioblastoma. 37 Therefore, eliminating glioma cell stemness is one of the critical strategies for clinical treatment. Some signaling molecules for the maintenance of stemness, such as Hedgehog, CD133, and NF‐κB, have been confirmed as potential therapeutic targets.…”

Molecular mechanism(s) of regulations of cancer stem cell in brain cancer propagation

“…These cells are also learned to possess resistance against chemo-and radiotherapies. 17,18 2 | FACTORS ASSOCIATED WITH BRAIN TUMOR AND BRAIN CSCS…”