Histological Characterization of the Tumorigenic “Peri-Necrotic Niche” Harboring Quiescent Stem-Like Tumor Cells in Glioblastoma

Ishii, Aya; Kimura, Tokuhiro; Sadahiro, Hirokazu; Kawano, Hiroyuki; Takubo, Keiyo; Suzuki, Michiyasu; Ikeda, Eiji

doi:10.1371/journal.pone.0147366

Cited by 59 publications

(66 citation statements)

References 49 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The literature published in recent years has revealed a growing focus on tumour cell dormancy, which is probably one of the main reasons for refractory to targeted or conventional therapies (7)(8)(9)(10). In glioma, the 'peri-necrotic niche' harbouring HIF-1α + quiescent stem-like cells have been proposed as candidates for long-term tumourigenic cells (11). For the enrichment in angiogenesis of upregulated DEGs, it is widely recognized that the extreme proliferation of new blood vessels in GBM is structurally and functionally abnormal and contributes to a hostile microenvironment (low oxygen tension and high interstitial fluid pressure) that selects for a more malignant phenotype with increasing morbidity and mortality (12)(13)(14).…”

Section: Discussionmentioning

confidence: 99%

Tumour cell dormancy as a contributor to the reduced survival of GBM patients who received standard therapy

Tong

Liu

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is a fatal cancer with varying life expectancy, even for patients undergoing the same standard therapy. Identification of differentially expressed genes in GBM patients with different survival rates may benefit the development of effective therapeutic strategies. In the present study, key pathways and genes correlated with survival in GBM patients were screened with bioinformatic analysis. Included in the study were 136 eligible patients who had undertaken surgical resection of GBM followed by temozolomide (TMZ) chemoradiation and long-term therapy with TMZ. A total of 383 differentially expressed genes (DEGs) related to GBM survival were identified. Gene Ontology and pathway enrichment analysis as well as hub gene screening and module analysis were performed. As expected, angiogenesis and migration of GBM cells were closely correlated with a poor prognosis. Importantly, the results also indicated that cell dormancy was an essential contributor to the reduced survival of GBM patients. Given the lack of specific targeted genes and pathways known to be involved in tumour cell dormancy, we proposed enriched candidate genes related to the negative regulation of cell proliferation, signalling pathways regulating pluripotency of stem cells and neuroactive ligand-receptor interaction, and 3 hub genes (FTH1, GRM1 and DDIT3). Maintaining persistent cell dormancy or preventing tumour cells from entering dormancy during chemoradiation should be a promising therapeutic strategy.

show abstract

Section: Discussionmentioning

confidence: 99%

Tumour cell dormancy as a contributor to the reduced survival of GBM patients who received standard therapy

Tong

Liu

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…3,8 A number of studies of perivascular niches have histological or histochemical images. 7,[65][66][67][68][69] Figures 3-5 show the relevant images. The vessels in the center of the perivascular niches have in all four cases a diameter that is too large and walls that are too thick for capillaries.…”

Section: Vessel Type In Perivascular Gsc Nichesmentioning

confidence: 99%

Glioma Stem Cell Niches in Human Glioblastoma Are Periarteriolar

Hira

Aderetti

Noorden

2018

J Histochem Cytochem.

View full text Add to dashboard Cite

Survival of primary brain tumor (glioblastoma) patients is seriously hampered by glioma stem cells (GSCs) that are distinct therapy-resistant self-replicating pluripotent cancer cells. GSCs reside in GSC niches, which are specific protective microenvironments in glioblastoma tumors. We have recently found that GSC niches are hypoxic periarteriolar, whereas in most studies, GSC niches are identified as hypoxic perivascular. The aim of this review is to critically evaluate the literature on perivascular GSC niches to establish whether these are periarteriolar, pericapillary, perivenular, and/or perilymphatic. We found six publications showing images of human glioblastoma tissue containing perivascular GSC niches without any specification of the vessel type. However, it is frequently assumed that these vessels are capillaries which are exchange vessels, whereas arterioles and venules are transport vessels. Closer inspection of the figures of these publications showed vessels that were not capillaries. Whether these vessels were arterioles or venules was difficult to determine in one case, but in the other cases, these were clearly arterioles and their perivascular niches were similar to the periarteriolar niches we have found. Therefore, we conclude that in human glioblastoma tumors, GSC niches are hypoxic periarteriolar and are structurally and functionally look-alikes of hematopoietic stem cell niches in the bone marrow.

show abstract

“…The definition of a tumor is a mass of cells that proliferate without relation to pattern or rate of the growth of the part in which it is located. This unlimited cellular growth may lead to the development of malignant properties, including invasion of surrounding tissues and metastasis to other organs [ 44 ]. In this study, we concluded from the following observations that none of the transplanted cells developed into malignant tumors.…”

Section: Discussionmentioning

confidence: 99%

Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases

et al. 2016

Self Cite

View full text Add to dashboard Cite

The risk of tumorigenicity is a hurdle for regenerative medicine using induced pluripotent stem cells (iPSCs). Although teratoma formation is readily distinguishable, the malignant transformation of iPSC derivatives has not been clearly defined due to insufficient analysis of histology and phenotype. In the present study, we evaluated the histology of neural stem/progenitor cells (NSPCs) generated from integration-free human peripheral blood mononuclear cell (PBMC)-derived iPSCs (iPSC-NSPCs) following transplantation into central nervous system (CNS) of immunodeficient mice. We found that transplanted iPSC-NSPCs produced differentiation patterns resembling those in embryonic CNS development, and that the microenvironment of the final site of migration affected their maturational stage. Genomic instability of iPSCs correlated with increased proliferation of transplants, although no carcinogenesis was evident. The histological classifications presented here may provide cues for addressing potential safety issues confronting regenerative medicine involving iPSCs.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0265-8) contains supplementary material, which is available to authorized users.

show abstract

Histological Characterization of the Tumorigenic “Peri-Necrotic Niche” Harboring Quiescent Stem-Like Tumor Cells in Glioblastoma

Cited by 59 publications

References 49 publications

Tumour cell dormancy as a contributor to the reduced survival of GBM patients who received standard therapy

Tumour cell dormancy as a contributor to the reduced survival of GBM patients who received standard therapy

Glioma Stem Cell Niches in Human Glioblastoma Are Periarteriolar

Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases

Contact Info

Product

Resources

About