The optimized priming effect of FGF-1 and FGF-2 enhances preadipocyte lineage commitment in human adipose-derived mesenchymal stem cells.

The cell-assisted lipotransfer technique, integrating adipose-derived mesenchymal stem cells (ADMSCs), has transformed lipofilling, enhancing fat graft viability. However, the multipotent nature of ADMSCs poses challenges. To improve safety and graft vitality and to reduce unwanted lineage differentiation, this study refines the methodology by priming ADMSCs into preadipocytes-unipotent, self-renewing cells.

A niche-mimicking polymer hydrogel-based approach to identify molecular targets for tackling human pancreatic cancer stem cells.

Background: Pancreatic adenocarcinoma (PAAD) is one of the most fatal human cancers, but effective therapies remain to be established. Cancer stem cells (CSCs) are highly resistant to anti-cancer drugs and a deeper understanding of their microenvironmental niche has been considered important to provide understanding and solutions to cancer eradication. However, as the CSC niche is composed of a wide variety of biological and physicochemical factors, the development of multidisciplinary tools that recapitulate their complex features is indispensable.

Cancer ego-system in glioma: an iron-replenishing niche network systemically self-organized by cancer stem cells.

For all living organisms, the adaptation to outside environments is an essential determinant to survive natural and artificial selections and to sustain the whole ecosystem intact with functional biodiversity. Likewise, cancer cells have similar characteristics that evade not only stresses from the host-internal innate and adaptive immune systems but also those from host-externally administered therapeutic interventions. Such selfish characteristics of cancer cells lead to the formation of cancerous ecosystem with a wide variety of phenotypic heterogeneity, which should be called cancer "egosystem" from the host point of view.

Therapy-resistant nature of cancer stem cells in view of iron metabolism.

Due to increased resistance to standard chemo/radiotherapies and relapse, highly tumorigenic cancer stem cells (CSCs) have been proposed as a promising target for the development of effective cancer treatments. In order to develop innovative cancer therapies that target CSCs, much attention has focused on the iron metabolism of CSCs, which has been considered to contribute to self-renewal of CSCs. Here, we review recent advances in iron metabolism and conventional iron metabolism-targeted cancer therapies, as well as therapy resistance of CSCs and potential treatment options to overcome them, which provide important insights into therapeutic strategies against intractable cancers.

Cancer Stem Cell-Associated Immune Microenvironment in Recurrent Glioblastomas.

Glioblastoma multiforme (GBM) is the most incurable tumor (due to the difficulty in complete surgical resection and the resistance to conventional chemo/radiotherapies) that displays a high relapse frequency. Cancer stem cells (CSCs) have been considered as a promising target responsible for therapy resistance and cancer recurrence. CSCs are known to organize a self-advantageous microenvironment (niche) for their maintenance and expansion.

Glioma cells remotely promote erythropoiesis as a self-expanding strategy of cancer stem cells.

Cancer stem cells are a promising target for cancer eradication due to their responsibility for therapy-resistance and cancer recurrence. Previously, we have demonstrated that glioma stem cells (GSCs) recruit and induce the differentiation of bone marrow (BM) monocytes into tumor-infiltrating macrophages, which phagocytose hemorrhaged erythrocytes and store GSC-beneficial iron in mouse xenografts, suggesting a self-expanding strategy of GSCs that exploits host hematopoiesis of myeloid cells. However, it remains unclear whether a self-advantageous effect of GSCs also occurs on erythroid cells during glioma development.

Difference in the malignancy between RAS and GLI1-transformed astrocytes is associated with frequency of p27-positive cells in xenograft tissues.

We demonstrate that the introduction of GLI1 is sufficient for immortalized human astrocytes to be transformed whereas FOXM1 fails to induce malignant transformation, suggesting differences between GLI1 and FOXM1 in terms of transforming ability despite both transcription factors being overexpressed in malignant gliomas. Moreover, in investigations of mechanisms underlying relatively less-malignant features of GLI1-transformed astrocytes, we found that p27-positive cells were frequently observed in xenografts derived from GLI1-transformed astrocytes compared to those from RAS-transformed cells. As shRNA-mediated knockdown of p27 accelerates tumor progression of GLI1-transformed astrocytes, downregulation of p27 contributes to malignant features of transformed astrocytes.

YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer.

Y-box binding protein 2 (YBX2) has been associated with the properties of both germ cells and cancer cells. We hypothesized that YBX2 might contribute to the characteristics of cancer stem cells (CSCs). In this study, we clarified the function of YBX2 in endometrial cancer stem cells.

Glioma progression and recurrence involving maintenance and expansion strategies of glioma stem cells by organizing self-advantageous niche microenvironments.

Due to the nature of enhanced resistance to conventional chemo/radiotherapies and metastasis, highly tumorigenic cancer stem cells (CSCs) have been proposed as a promising target for cancer eradication. To tackle the therapeutic difficulties of cancers involving CSCs, extensive research efforts have been directed toward understanding the extracellular microenvironments of CSCs, i.e.

Glioma stem cell (GSC)-derived autoschizis-like products confer GSC niche properties involving M1-like tumor-associated macrophages.

Spontaneous necrosis is a defining feature of glioblastomas (GBMs), the most malignant glioma. Despite its strong correlations with poor prognosis, it remains unclear whether necrosis could be a possible cause or mere consequence of glioma progression. Here we isolated a particular fraction of necrotic products spontaneously arising from glioma cells, morphologically and biochemically defined as autoschizis-like products (ALPs).

Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-defined glioma stem cells by iron chelation.

Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection.

Requirement of ABC transporter inhibition and Hoechst 33342 dye deprivation for the assessment of side population-defined C6 glioma stem cell metabolism using fluorescent probes.

Background: Elucidating the precise properties of cancer stem cells (CSCs) is indispensable for the development of effective therapies against tumors, because CSCs are key drivers of tumor development, metastasis and relapse. We previously reported that the Hoechst 33342 dye-low staining side population (SP) method can enrich for CSCs in the C6 glioma cell line, and that the positively stained main population (MP) cells are non-CSCs. Presence of cancer stem-like SP cells is reported in various types of cancer.

A Synthetic Polymer Scaffold Reveals the Self-Maintenance Strategies of Rat Glioma Stem Cells by Organization of the Advantageous Niche.

Cancer stem cells (CSCs) are believed to be maintained within a microenvironmental niche. Here we used polymer microarrays for the rapid and efficient identification of glioma CSC (GSC) niche mimicries and identified a urethane-based synthetic polymer, upon which two groups of niche components, namely extracellular matrices (ECMs) and iron are revealed. In cultures, side population (SP) cells, defined as GSCs in the rat C6 glioma cell line, are more efficiently sustained in the presence of their differentiated progenies expressing higher levels of ECMs and transferrin, while in xenografts, ECMs are supplied by the vascular endothelial cells (VECs), including SP cell-derived ones with distinctively greater ability to retain xenobiotics than host VECs.

Induction of protumoral CD11c(high) macrophages by glioma cancer stem cells through GM-CSF.

Cancer stem cells (CSCs) are maintained under special microenvironment called niche, and elucidation and targeting of the CSC niche will be a feasible strategy for cancer eradication. Tumor-associated macrophages (TAMs) are known to be involved in cancer progression and thus can be a component of CSC niche. Although TAMs are known to play multiple roles in tumor progression, involvement of CSCs in TAM development fully remains to be elucidated.

Up-regulation of lymphocyte antigen 6 complex expression in side-population cells derived from a human trophoblast cell line HTR-8/SVneo.

The continual proliferation and differentiation of trophoblasts are critical for the maintenance of pregnancy. It is well known that the tissue stem cells are associated with the development of tissues and pathologies. It has been demonstrated that side-population (SP) cells identified by fluorescence-activated cell sorting (FACS) are enriched with stem cells.

A growth-promoting signaling component cyclin D1 in neural stem cells has antiastrogliogenic function to execute self-renewal.

Self-renewing proliferation of neural stem cells (NSCs) is intimately linked to the inhibition of neuronal and glial differentiation, however, their molecular linkage has been poorly understood. We have proposed a model previously explaining partly this linkage, in which fibroblast growth factor 2 (FGF2) and Wnt signals cooperate to promote NSC self-renewal via β-catenin accumulation, which leads to the promotion of proliferation by lymphoid enhancer factor (LEF)/T-cell factor (TCF)-mediated cyclin D1 expression and at the same time to the inhibition of neuronal differentiation by β-catenin-mediated potentiation of Notch signaling. To fully understand the mechanisms underlying NSC self-renewal, it needs to be clarified how these growth factor signals inhibit glial differentiation as well.

The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells.

Goals: We previously demonstrated that side-population (SP) cells in human endometrial cancer cells (Hec1 cells) and in rat endometrial cells expressing oncogenic human K-Ras protein (RK12V cells) have features of cancer stem cells (CSCs). Hec1-SP cells showed enhanced migration and the potential to differentiate into the mesenchymal cell lineage. In this study, we analyzed the association of the epithelial-mesenchymal transition (EMT) with the properties of these endometrial CSCs.

Gene Regulation of Prominin-1 (CD133) in Normal and Cancerous Tissues.

A pentaspan membrane glycoprotein prominin-1 (frequently called CD133 in human) is widely used as a surface marker to identify and isolate normal stem/progenitor cells from various organs, although it is also expressed in some types of differentiated cells. Since CD133 was identified as a universal marker to isolate cancer stem cells (CSCs) in tumors derived from multiple tissues, much attention has been directed toward the relationship between its gene regulation and identity of CSCs (i.e.

CD133 negatively regulates tumorigenicity via AKT pathway in synovial sarcoma.

Synovial sarcoma (SS) is an aggressive tumor that accounts for almost 10% of all soft tissue sarcomas. In this study, we found the expression of CD133 in human SS specimens, thus, we focused on the function of CD133 in SS. Separation of the CD133-positive and -negative subpopulations in SS cell lines clarified that the CD133-negative subpopulation exhibited enhanced growth and hyperphosphorylation of AKT.

A case of clear cell variant of solid-pseudopapillary tumor of the pancreas in an adult male patient.

A clear cell variant of solid-pseudopapillary tumor (SPT) of the pancreas was initially reported in 2006 as a tumor that arose in the pancreatic body and tail in young adults; to date, only 4 cases of this entity have been reported. Here, we present the case of a 58-year-old man with clear cell variant of SPT with distinctive clinicopathologic features. The tumor was well demarcated, was 2.

Analysis of an alternative human CD133 promoter reveals the implication of Ras/ERK pathway in tumor stem-like hallmarks.

Background: An increasing number of studies support the presence of stem-like cells in human malignancies. These cells are primarily responsible for tumor initiation and thus considered as a potential target to eradicate tumors. CD133 has been identified as an important cell surface marker to enrich the stem-like population in various human tumors.

Human synovial sarcoma proto-oncogene Syt is essential for early embryonic development through the regulation of cell migration.

SYT-SSX protein, resulted from chromosomal translocation, causes synovial sarcoma, which is a malignant tumor accounting for 10% of soft tissue sarcoma. However, biological functions of SYT (synovial sarcoma translocation), also known as SS18, are largely unclear, whereas it has been proven that Syt-null mice die at early stages of embryonic development. Here, we generated Syt-deficient mice and confirmed the reported phenotypes, including growth retardation, open neural tube and haplo-insufficient lethality, and therefore, there is no doubt that Syt is essential for embryonic development.

Promoter hypomethylation regulates CD133 expression in human gliomas.

Brain tumor-initiating cells (BTICs) have been enriched using antibodies against the cell surface protein CD133; however, the biological relevance and the regulatory mechanism of CD133 expression in human gliomas are not yet understood. In this study, we initially demonstrated that CD133 was overexpressed in high-grade human glioblastomas where CD133-positive cells were focally observed as a micro-cluster. In addition, CD133 transcripts with exon 1A, 1B, or 1C were predominantly expressed in glioblastomas.

A case of cerebral ganglioneuronal tumor in the parietal lobe of an adult.

Central nervous system (CNS) neuroblastoma/ganglioneuroblastoma is one of the embryonal tumors with neuronal differentiation found in young adults, but it is most common in children, especially in those below the age of 5 years, whereas extraventricular neurocytoma, a rare neuroepithelial tumor with neuronal differentiation, mostly affects young adults. Here we present a rare case of cerebral ganglioneuronal tumor that occurred in a 32-year-old woman. The patient suffered from tonic convulsion, and computed tomography demonstrated a well-demarcated, round tumor 3.

Oligodendrocyte lineage transcription factor 2 inhibits the motility of a human glial tumor cell line by activating RhoA.

The basic helix-loop-helix transcription factor, oligodendrocyte lineage transcription factor 2 (OLIG2), is specifically expressed in the developing and mature central nervous system and plays an important role in oligodendrogenesis from neural progenitors. It is also expressed in various types of glial tumors, but rarely in glioblastoma. Although we previously showed that OLIG2 expression inhibits glioma cell growth, its role in tumorigenesis remains incompletely understood.