Tumor Microenvironment — Perivascular and Perinecrotic Niches

Schiffer, Davide; Mellai, Marta; Annovazzi, Laura; Casalone, Cristina; Cassoni, Paola

doi:10.5772/58962

Cited by 9 publications

(12 citation statements)

References 191 publications

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“…These are believed to occur everywhere in the tumor [ 63 ] or to be heterogeneously distributed within it [ 64 , 65 ]. Regardless of their origin [ 25 , 55 , 66 ], our findings demonstrate a molecular and stemness gradient from the highest malignant tumor areas to the periphery [ 67 , 68 ].…”

Section: Discussionmentioning

confidence: 94%

Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and genotype in glioblastoma

et al. 2017

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Glioblastoma (GB) is a highly heterogeneous tumor. In order to identify in vivo the most malignant tumor areas, the extent of tumor infiltration and the sites giving origin to GB stem cells (GSCs), we combined positron emission tomography/computed tomography (PET/CT) and conventional and advanced magnetic resonance imaging (MRI) with histology, immunohistochemistry and molecular genetics. Prior to dura opening and tumor resection, forty-eight biopsy specimens [23 of contrast-enhancing (CE) and 25 of non-contrast enhancing (NE) regions] from 12 GB patients were obtained by a frameless image-guided stereotactic biopsy technique.The highest values of 2-[18F]-fluoro-2-deoxy-D-glucose maximum standardized uptake value (18F-FDG SUVmax), relative cerebral blood volume (rCBV), Choline/Creatine (Cho/Cr), Choline/N-acetylaspartate (Cho/NAA) and Lipids/Lactate (LL) ratio have been observed in the CE region. They corresponded to the most malignant tumor phenotype, to the greatest molecular spectrum and stem cell potential. On the contrary, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in the CE region were very variable.18F-FDG SUVmax, Cho/Cr and Cho/NAA ratio resulted the most suitable parameters to detect tumor infiltration. In edematous areas, reactive astrocytes and microglia/macrophages were influencing variables.Combined MRI and 18F-FDG PET/CT allowed to recognize the specific biological significance of the different identified areas of GB.

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Section: Discussionmentioning

confidence: 94%

Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and genotype in glioblastoma

et al. 2017

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“…The GSC origin is a widely shared hypothesis [28]. We have previously hypothesized that they might originate from dedifferentiation of tumor cells that takes place in the most malignant tumor areas under the influence of tumor microenvironment [29] with its crucial perivascular and perinecrotic niches.…”

Section: Stem Cell Research and Therapymentioning

confidence: 99%

Glioblastoma Stem Cells: Conversion or Reprogramming from Tumor Non- Stem Cells?

Schiffer¹,

Annovazzi²,

Cassoni³

et al. 2015

J Stem Cell Res Ther

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It is widely accepted that gliomas origin from immature glia and the most important hypothesis is that this origin is from glioblastoma stem cells (GSCs). GSCs are responsible for tumor growth, proliferation, therapy resistance and recurrence. They may represent transformed normal neural stem cells (NSCs), embryonically regressed adult glia or, simply, a functional status that could be regulated by the tumor microenvironment. Objective of the work is to interpret all the immunohistochemical, genetic and in vitro culture features of primary tumors and cell lines in favor of the above mentioned hypothesis on the functional status and microenvironment. A series of glioblastomas (GBMs) have been studied after stereotactic biopsies for expression of stemness and differentiation antigens, genetic aberrations and stem cell generation potential by immunohistochemical, immunofluorescence, molecular genetics methods. Perivascular and perinecrotic niches are the crucial points where microenvironment exerts its influence. The most malignant regions of GBM contain hyperproliferating areas expressing stemness antigens, such as Nestin, SOX2, CD133 and almost no differentiation antigens and show a high proliferation index. Circumscribed necroses develop within these areas by ischemia due to the imbalance between the high proliferation rate of tumor cells and the low one of endothelial cells. Perinecrotic GSCs are interpreted as elicited by hypoxia through HIF-1/2 constituting thus a niche. The hypothesis can be formulated that the stem cell status is a functional one that can be reached by dedifferentiated tumor cells through embryonic regression and that GSCs surrounding circumscribed necroses may of course represent a niche, but they are the residue of GCSs/progenitors originally populating the hyperproliferating areas. A conversion of tumor non-stem cells into tumor stem cells is possible, as well as reprogramming of tumor cells due to the microenvironment regulation through its intrinsic and extrinsic signaling. This hypothesis could influence the therapeutic strategies addressed to annihilate GSCs.

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“…GSCs/progenitors activate endothelial cells for angiogenesis by VEGF [16] and endothelial cells keep GSC/progenitor stemness and migration capacity by Notch signaling and NO [2,5,8,17] that condition tumor progression [18]. The perivascular position of GSCs/progenitors is the consequence of the occurrence of angiogenesis in high infiltration and hyper-proliferation areas, composed mainly by GSCs/progenitors [19][20][21] and regulated by tumor microenvironment. From the reciprocal signaling exchange between endothelial cells and GSCs/progenitors tumor progression and angiogenesis are triggered [22] with the latter originating from the switch from an avascular to a vascular state with matrix degradation and basal membrane dissolution.…”

Section: Discussionmentioning

confidence: 99%

Perivascular niches as points of the utmost expression of tumor microenvironment

Annovazzi¹,

Mellai²,

Bisogno³

et al. 2017

Hematol Med Oncol

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Tumor Microenvironment — Perivascular and Perinecrotic Niches

Cited by 9 publications

References 191 publications

Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and genotype in glioblastoma

Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and genotype in glioblastoma

Glioblastoma Stem Cells: Conversion or Reprogramming from Tumor Non- Stem Cells?

Perivascular niches as points of the utmost expression of tumor microenvironment

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