Perspectives on Brain Tumor Formation Involving Macrophages, Glia, and Neural Stem

Seyfried, Thomas N.

doi:10.1353/pbm.2001.0035

Cited by 48 publications

(72 citation statements)

References 84 publications

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“…This process involves release of inflammatory cytokines and phagocytosis of debris. 48 Following these activities, macrophages intravasate back into the circulation where they take up residence in the lymph nodes and participate in the immune response. 49 These characteristics of The ganglioside standards were from VM mouse brain, B, and purified GM3 and were visualized with the resorcinol spray.…”

Section: Discussionmentioning

confidence: 99%

“…1,[57][58][59][60][61] Rather, macrophages are generally considered part of the tumor stroma that either inhibit or facilitate tumor growth. 48,[62][63][64] A macrophage origin of metastatic cancer stands apart from more widely recognized origins involving epithelialmesenchymal transitions following random somatic mutations. 1,57,65 As macrophages/microglia are mesenchymal cells, 66,67 our findings support a mesenchymal association with metastatic cancer.…”

Section: Discussionmentioning

confidence: 99%

“…It is also well-documented that GBM contain cells with multiple macrophage-like morphologies to include small round cells and multinucleated giant cells. 48,71,74 It has been difficult, however, to determine with certainty the origin of all microglial/macrophagelike cells within human GBM. 48,75 We suggest that some of these macrophage-like cells are part of the tumor and are the most invasive cells of GBM.…”

Section: Discussionmentioning

confidence: 99%

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Metastatic cancer cells with macrophage properties: Evidence from a new murine tumor model

Huysentruyt

Mukherjee

Banerjee

et al. 2008

Intl Journal of Cancer

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154

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Metastasis is the process by which cancer cells disseminate from the primary neoplasm and invade surrounding tissue and distant organs, and is the primary cause of morbidity and mortality for cancer patients. Most conventional cancer therapies are ineffective in managing tumor metastasis. This has been due in large part to the absence of in vivo metastatic models that represent the full spectrum of metastatic disease. Here we identify 3 new spontaneously arising tumors in the inbred VM mouse strain, which has a relatively high incidence of CNS tumors. Two of the tumors (VM-M2 and VM-M3) reliably expressed all of the major biological processes of metastasis to include local invasion, intravasation, immune system survival, extravasation and secondary tumor formation involving liver, kidney, spleen, lung and brain. Metastasis was assessed through visual organ inspection, histology, immunohistochemistry and bioluminescence imaging. The metastatic VM tumor cells also expressed multiple properties of macrophages including morphological appearance, surface adhesion, phagocytosis, total lipid composition (glycosphingolipids and phospholipids) and gene expression (CD11b, Iba1, F4/80, CD68, CD45 and CXCR4). The third tumor (VM-NM1) grew rapidly and expressed properties of neural stem/progenitor cells, but was neither invasive nor metastatic. Our data indicate that spontaneous brain tumors can arise from different cell types in VM mice and that metastatic cancer can represent a disease of macrophage-like cells similar to those described in several human metastatic cancers.The new VM tumor model will be useful for defining the biological processes of cancer metastasis and for evaluating potential therapies for tumor management. ' 2008 Wiley-Liss, Inc.Key words: metastasis; microglia; gangliosides; neural stem cell; glioblastoma Metastasis is the process by which cancer cells disseminate from the primary neoplasm and invade surrounding tissue and distant organs and is the primary cause of morbidity and mortality for cancer patients. This process involves cancer cell detachment from the primary tumor, intravasation into the circulation, evasion of immune attack, extravasation at distant capillary beds and invasion and proliferation in distant organs. [1][2][3] In addition, the metastatic cells establish a microenvironment facilitating colonization (angiogenesis and further proliferation), resulting in macroscopic malignant secondary tumors.1-4 Metastatic cells preferentially invade those organs (lymph nodes, lung, liver, brain, bone, pleura and peritoneum) that promote tumor cell growth and survival consistent with the ''seed and soil'' hypothesis. 1,5,6 The metastatic and invasive potential of cancer cells is often correlated with abnormalities in phospholipids and in cell-surface glycolipids, which contribute to tumor progression.7-10 Hence, aberrant cellular migration and proliferation characterize the metastatic phenomenon.In this study, we analyzed the morphological, behavioral, biochemical and genetic properties of 3 n...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Metastatic cancer cells with macrophage properties: Evidence from a new murine tumor model

Huysentruyt

Mukherjee

Banerjee

et al. 2008

Intl Journal of Cancer

Self Cite

154

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“…DR reduces mouse brain tumour angiogenesis and growth P Mukherjee et al the proangiogenic and inflammatory properties of activated glia and macrophages (Seyfried, 2001). Indeed, the degree of tumour angiogenesis and malignancy is generally correlated with the number and activation state of tumour-associated macrophages and microglia (Wood and Morantz, 1979;Roggendorf et al, 1996;Nishie et al, 1999;Polverini, 1999;Badie and Schartner, 2000).…”

Section: Discussionmentioning

confidence: 99%

Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model

et al. 2002

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Diet and lifestyle produce major effects on tumour incidence, prevalence, and natural history. Moderate dietary restriction has long been recognised as a natural therapy that improves health, promotes longevity, and reduces both the incidence and growth of many tumour types. Dietary restriction differs from fasting or starvation by reducing total food and caloric intake without causing nutritional deficiencies. No prior studies have evaluated the responsiveness of malignant brain cancer to dietary restriction. We found that a moderate dietary restriction of 30 -40% significantly inhibited the intracerebral growth of the CT-2A syngeneic malignant mouse astrocytoma by almost 80%. The total dietary intake for the ad libitum control group (n=9) and the dietary restriction experimental group (n=10) was about 20 and 13 Kcal day 71 , respectively. Overall health and vitality was better in the dietary restriction-fed mice than in the ad libitum-fed mice. Tumour microvessel density (Factor VIII immunostaining) was two-fold less in the dietary restriction mice than in the ad libitum mice, whereas the tumour apoptotic index (TUNEL assay) was three-fold greater in the dietary restriction mice than in the ad libitum mice. CT-2A tumour cellinduced vascularity was also less in the dietary restriction mice than in the ad libitum mice in the in vivo Matrigel plug assay. These findings indicate that dietary restriction inhibited CT-2A growth by reducing angiogenesis and by enhancing apoptosis. Dietary restriction may shift the tumour microenvironment from a proangiogenic to an antiangiogenic state through multiple effects on the tumour cells and the tumour-associated host cells. Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers.

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“…A sampling of human metastatic cancers with properties of macrophage-like cells include brain [204,[217][218][219][220], breast [221][222][223][224][225], lung [202,[225][226][227][228][229], skin [203,205,209,210,[230][231][232][233], gastric [234], colon [235,236], pancreas [237,238], bladder [239], kidney [240], ovarian [241,242], and muscle [243,244]. It is important to mention that these macrophage properties are expressed in the tumor cells themselves and are not to be confused with similar properties expressed in the non-neoplastic TAM, which are also present in tumors and can facilitate tumor progression [190,213,215,216,245]. Poor prognosis is generally associated with those cancers that display characteristics of macrophages [210,221].…”

Section: Invasion and Metastasismentioning

confidence: 99%

Cancer as a Metabolic Disease

Seyfried¹

2012

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194

291

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Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention.

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Perspectives on Brain Tumor Formation Involving Macrophages, Glia, and Neural Stem

Cited by 48 publications

References 84 publications

Metastatic cancer cells with macrophage properties: Evidence from a new murine tumor model

Metastatic cancer cells with macrophage properties: Evidence from a new murine tumor model

Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model

Cancer as a Metabolic Disease

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