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Results for “Cellular Microenvironment”

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At least 919 records · Page 51Linked to original sources

PubMed2005

Intestinal metaplasia with a high salt diet induces epithelial proliferation and alters cell composition in the gastric mucosa of mice.

Intestinal metaplasia of the gastric mucosa is an important component in the pathway to adenocarcinoma. The mechanisms that induce the progression from intestinal metaplasia to cancer have not been elucidated. High dietary salt has been known as one of the risk factors for gastric cancer development in humans. Therefore, we investigated the role of high salt diet on gastric epithelial cell proliferation and differentiation, using our mouse model that ectopically expressed Cdx2 homeodomain transcription factor and induced an intestinal metaplastic phenotype in the gastric epithelia. Sixty Cdx2 transgenic and sixty age-matched wild-type littermates were studied. Fifty-percent Cdx2 transgenic and wild type mice were administered a high-salt diet and the other fifty-percent was fed a standard diet starting at 12 weeks after birth. At 10, 20 and 40 weeks after initiation of the diets, histopathological changes were determined by Hemotoxylin and Eosin, alcian blue, and periodic acid-Schiff (PAS) staining. Cell types and cell kinetics were assessed by immunohistochemistry. At 52 weeks, significant alterations in pathology were observed in the Cdx2 transgenic mice fed a high-salt diet, including elongation of gastric pits, reduction of the glandular zone in the gastric corpus, and deepening of glands in the antrum. In the Cdx2 transgenic mice fed a high salt diet, the parietal and chief cells were significantly decreased in the gastric corpus. A significant increase in cell proliferation and apoptosis in the corpus and antrum were observed in Cdx2 transgenic mice fed a high-salt diet as compared to wild-type littermates. Taken together, these data implicate that intestinal metaplasia in concert with a high-salt diet induces epithelial proliferation, apoptosis, and alters cellular types in the gastric mucosa of mice. Alteration in the composition of the gastric epithelium may play a role in influencing the microenvironment to engender susceptibility to carcinogens.

Animals↗

PubMed2006

A short primer on early molecular and cellular events in thymus organogenesis and replacement.

Haematopoietic precursors have to undergo a complex series of maturational steps in the thymus before they exit into the periphery as functional T lymphocytes. Thymic stroma cells, the majority being of epithelial origin, provide the functional partners for the maturational progression along this differentiation pathway. Here we review some of the molecular and cellular mechanisms that account for thymus organogenesis and discuss a strategy to use thymic epithelial precursor cells for the regeneration of the thymic microenvironment.

Autoantigens↗

PubMed1991

Expression of laminin and its receptor LBP-32 in human and rat hepatoma cells.

Dramatic cellular changes that occur during hepatocarcinogenesis are associated with major alterations in extracellular matrix formation and in the relationships between cells and their microenvironment. We have studied the expression of laminin, the major noncollagenous glycoprotein of basement membrane, and the laminin receptor 32 kD laminin-binding protein in two rat (Faza 967 and HTC) and two human (HepG2 and HBGC2) hepatoma cell lines that express a variety of liver-specific functions. Laminin was found in the rough endoplasmic reticulum of these cells when the indirect immunoperoxidase method and electron microscopic examination were used. Radiolabeled laminin, immunoprecipitated from both media and cell extracts, was resolved by electrophoresis on sodium dodecyl sulfate gel in two major polypeptides that comigrated with the A and B subunits from Engelbreth-Holm-Swarm tumor laminin. Immunoblot analysis showed that the Mr = 400,000 polypeptide did not correspond to the A subunit of laminin. Northern blot analyses demonstrated large amounts of B1 and B2 mRNAs but no A chain mRNA. We conclude that the tumor cells produce the laminin B chains only. In contrast, normal adult hepatocytes from either man or rat lacked laminin mRNAs, whereas in 1-day primary culture, B chain mRNAs became detectable. The steady-state level of 32 kD laminin-binding protein mRNA was 10-fold and threefold higher in rat hepatoma cells than in freshly isolated and 1-day cultured normal rat hepatocytes, respectively. In human hepatocytes, the steady-state levels of 32 kD laminin-binding protein mRNAs varied depending on the donor and never reached the level of the human hepatoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Late failure of autologous marrow grafts in lethally irradiated dogs given anti-class II monoclonal antibody.

We established a model of canine marrow autografts after 9.2 Gy total body irradiation (TBI) to study the role of class II antigens in hematopoietic stem cell growth and differentiation. Twenty dogs were given 9.2 Gy TBI, marrow, and intravenous (IV) murine anti-class II monoclonal antibody (MoAb). Infusion of 0.6 mg/kg/d of MoAb H81.98.21, an IgG2a reactive with HLA-DR, on days 0 to 4 after TBI did not prevent initial engraftment, but dogs died with late graft failure. MoAb B1F6, an IgG2a reactive with HLA-DR + DP, had no adverse effect on engraftment, although both MoAbs detect antigens on stem cells. The critical time for the effect of MoAbs is the first 4 days after transplantation. Our findings argue against several pathogenetic mechanisms, including removal of MoAb-coated stem cells by the reticuloendothelial system (RES), canine complement-mediated cytotoxic effects on stem cells, antibody-dependent cellular cytotoxicity, and inactivation of MoAb-coated cells by dog anti-mouse antibody. To distinguish between MoAb-induced damage to microenvironment (ME)/accessory cells (AC) and late graft failure from a lack of pluripotent stem cells, three dogs were given TBI, a marrow autograft, and MoAb H81.98.21 on days 0 to 4; one, given thoracic duct cells on day 6, developed graft failure; the other two, given marrow depleted of AC by L-leucyl L-leucine o-methyl ester (Leu-Leu-OMe), had sustained grafts. Findings support the notion that originally transplanted pluripotent stem cells are no longer present on day 6 and that the ME is functional and able to support newly injected stem cells.

Animals↗

PubMed2005

Glial influences on neural stem cell development: cellular niches for adult neurogenesis.

Neural stem cells continually generate new neurons in very limited regions of the adult mammalian central nervous system. In the neurogenic regions there are unique and highly specialized microenvironments (niches) that tightly regulate the neuronal development of adult neural stem cells. Emerging evidence suggests that glia, particularly astrocytes, have key roles in controlling multiple steps of adult neurogenesis within the niches, from proliferation and fate specification of neural progenitors to migration and integration of the neuronal progeny into pre-existing neuronal circuits in the adult brain. Identification of specific niche signals that regulate these sequential steps during adult neurogenesis might lead to strategies to induce functional neurogenesis in other brain regions after injury or degenerative neurological diseases.

Animals↗

PubMed2000

Acidic pH inhibits non-MHC-restricted killer cell functions.

Immunotherapeutic strategies in advanced stages of solid tumors have generally met with little success. Various mechanisms have been discussed permitting the escape of tumor cells from an effective antitumoral immune response. Solid tumors are known to develop regions with acidic interstitial pH. In a recent study performed in the human system, we were able to demonstrate that non-MHC-restricted cytotoxicity is inhibited by an acidic microenvironment. To get more insight into the mechanisms leading to this reduced cytotoxic activity, we have now investigated the influence of an acidic extracellular pH (pH(e)) on the killing process in detail. Unstimulated PBMC and LAK cells were used as effector cells. Both populations are able to kill tumor cells in a MHC-independent manner via perforin/granzymes or TNFalpha, whereas only IL-2-activated cells can use the killing pathway via Fas/FasL. We studied the influence of a declining pH(e) on the different killing pathways against TNFalpha-sensitive and -resistant, as well as Fas-positive and -negative, target cells. Experiments in the absence of extracellular Ca(2+) were used to discriminate the Ca(2+)-dependent perforin-mediated killing. Here we show that the release of perforin/granzyme-containing granules, the secretion of TNFalpha, and also the cytotoxic action of Fas/FasL interaction or of membrane-bound TNFalpha were considerably inhibited by declining pH(e). Furthermore, the secretion of the activating cytokine IFNgamma, as well as the release of the down-regulating cytokines IL-10 and TGF-beta(1), was strictly influenced by surrounding pH. As a pH(e) of 5.8 resulted in a nearly complete loss of cytotoxic effector cell functions without affecting their viability, we investigated the influence of pH(e) on basic cellular functions, e.g. , mitochondrial activity and regulation of intracellular pH. We found an increasing inhibition of both functions with declining pH(e). Therefore, an acidic pH(e) obviously impairs fundamental cellular regulation, which finally prevents the killing process. In summary, our data show a strict pH(e) dependence of various killer cell functions. Thus, an acidic microenvironment within solid tumors may contribute to the observed immunosuppression in vivo, compromising antitumoral defense and immunotherapy in general, respectively.

Acids↗

PubMed2002

Challenges and opportunities for in vivo imaging in oncology.

Advances in genomics, proteomics and technology are changing medicine in fundamental ways. There are increasing clinical and laboratory requirements to obtain cellular and molecular information in vivo. This is particularly true in oncology, where the behavior of tumor cells is inextricably linked to their milieu. If cancer cells are removed from their microenvironment, their pattern of gene expression changes. Therefore, non-invasive, quantitative means of detecting gene and protein activity are essential. In vivo imaging is one methodology for achieving this. Marked advances in tracer methods for PET scanning or single-photon nuclear medicine techniques have occurred in the past few years. MRI contrast agents that reflect physiologic information are also being developed, although larger mass quantities of injectable material are required. The useful concept of "activatable agents" was pioneered in MRI. Similarly, ultrasound and computed tomography are being re-engineered to reflect information at the cellular level. In vivo optical imaging technologies have matured to the point where they are indispensable laboratory tools for small animal imaging. Human applications are in the feasibility testing stage, and the future for clinical optical imaging techniques looks bright. Merging these molecular imaging techniques with minimally or non-invasive image-guided therapeutic delivery techniques is a subsequent goal in the fight against cancer.

Humans↗

PubMed1997

Lipoprotein trafficking in vascular cells. Molecular Trojan horses and cellular saboteurs.

During the pathogenesis of atherosclerosis, inflammatory cells such as the monocyte-derived macrophage accumulate in the vessel wall where they release cytokines. Initially, cytokines may assist in CE removal of lipoprotein-derived cholesterol/CE hydrolysis to clear intracellular lipid. When plasma levels of LDL become elevated, the vessel wall becomes lipid-engorged over time because it is unable to traffick the large amounts of endocytosed LDL-CE from the cell. In addition, lipoprotein entrapment by the extracellular matrix can lead to the progressive oxidation of LDL because of the action of lipoxygenases, reactive oxygen species, peroxynitrite, and/or myeloperoxidase. A range of oxidized LDL species is thus generated, ultimately resulting in their delivery to vascular cells through several families of scavenger receptors (Fig 1). These molecular Trojan horses and cellular saboteurs once formed or deposited in the cell can contribute to, and participate in, formation of macrophage- and smooth muscle-derived foam cells. A lipid-enriched fatty streak along the vessel wall can ensue. In addition to foam cell development, products of LDL peroxidation may activate endothelial cells, increase smooth muscle mitogenesis, or induce apoptosis because of the effects of oxysterols and products of lipid peroxidation (Fig 1). Because antioxidant defenses may be limited in the microenvironment of the cell or within LDL, the oxidation process continues to progress. Enzymes associated with HDL such as PAF acetylhydrolase and paraoxonase can participate in the elimination of biologically active lipids, but diminished cellular antioxidant activity coupled with low levels of HDL may allow acceleration of the clinical course of vascular disease. There is still much to be learned about how modified LDL initiate cellular signals that lead to inflammation, mitosis, or cholesterol accumulation. The present challenges include elucidation of the key signaling events that regulate lipoprotein-derived cholesterol trafficking in the vessel wall, which can impact on the pathogenesis of vascular disease.

Arteries↗

PubMed2026

Construction and validation of a β-hydroxybutyrylation-related molecular model for predicting prognosis of papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) usually has a favorable prognosis, yet a subset of patients develops persistent, recurrent, or biologically aggressive disease. The clinical relevance of lysine β-hydroxybutyrylation (Kbhb)-related transcriptional programs in PTC remains unclear. Accordingly, this study aimed to characterize Kbhb-related molecular heterogeneity in PTC, construct a prognostic signature, and explore its association with the tumor microenvironment (TME). METHODS: Transcriptomic and clinical data from PTC samples within The Cancer Genome Atlas Thyroid Carcinoma (TCGA-THCA) cohort were analyzed to identify Kbhb-related differentially expressed genes (DEGs), define molecular subtypes, construct a prognostic signature, and characterize tumor microenvironmental features. Single-cell RNA-sequencing data from PTC were further used to explore the cellular distribution of representative genes. RESULTS: We identified 51 Kbhb-related DEGs in PTC and defined two Kbhb molecular subtypes. The Kbhb_C2 subtype showed shorter progression-free interval (PFI) and a more immune- and stroma-enriched microenvironment. A six-gene prognostic signature comprising TARID, CDSN, PIMREG, KLRC1, SYT13, and NPR3 was then established. High-risk patients had significantly worse PFI in the full, training, and testing cohorts, with 1-, 3-, and 5-year areas under the curve (AUCs) of 0.715, 0.793, and 0.771, respectively, in the full cohort. High-risk tumors also exhibited higher stromal, immune, and ESTIMATE scores, altered immune infiltration, and increased expression of multiple immune checkpoint molecules. Single-cell analysis confirmed distinct cell-type-specific expression patterns of representative genes. CONCLUSIONS: Kbhb-related transcriptional programs define clinically relevant molecular heterogeneity in PTC and are closely associated with prognosis and TME remodeling. The identified six-gene signature provides a biologically interpretable framework for risk stratification in PTC.

Papillary thyroid carcinoma (PTC)↗

PubMed2026

Oncogenic Mutations and Tumor Microenvironment Alterations in Diffuse Large B-Cell Lymphoma With Bulky Disease.

BACKGROUND: Bulky disease represents a clinically aggressive subset of diffuse large B-cell lymphoma (DLBCL) associated with adverse clinical outcomes. The aim of this study was to investigate the influence of oncogenic mutations and tumor microenvironment alterations on bulky disease in DLBCL. METHODS: We analyzed a cohort of 939 patients with newly diagnosed DLBCL. Using DNA (n = 934) and RNA (n = 524) sequencing, we compared oncogenic mutations and tumor microenvironment (TME) alterations based on tumor diameter, with cutoff values at 5.0 cm and 10.0 cm. Further stratification by mutations in key genes (CD58, STAT6, EBF1) correlated with tumor diameter revealed distinct transcriptomic and immunologic profiles. Subsequent single-cell RNA sequencing, guided by these mutational signatures, resolved the cellular heterogeneity within the TME. RESULTS: Integrative analysis revealed that tumor diameter correlated with increased incidence of mutations in CD58, STAT6, and EBF1; adverse genetic subtypes such as EZB-like MYC+ and TP53Mut; activation of oncogenic pathways (JAK/STAT, BCR, PI3K, and MYC); and an immunosuppressive tumor microenvironment. Notably, immune checkpoint molecules varied across the bulky stages, with CTLA-4, TIGIT, ICOS, and CD28 expression inversely correlated with tumor diameter, while CD70 and 4-1BBL expression positively correlated. Single-cell RNA sequencing further revealed mutation-specific tumor microenvironment insights. CD58-mutated tumor exhibited a profoundly immune-deserted microenvironment dominated by malignant B cells with minimal immune infiltration, whereas STAT6-mutated tumor was associated with increased fibroblasts and CD4 + T cells, particularly regulatory T cells (Treg) and Th1-like cells; EBF1-mutated tumor was characterized by increased proportions of malignant B cells. CONCLUSIONS: Collectively, our findings highlight the biological complexity of bulky disease, identifying candidate molecular targets and providing a biological framework for future therapeutic hypothesis generation in this clinically aggressive subset of DLBCL.

Humans↗

PubMed1997

Human T lymphocytes bind to germinal centers of human tonsils via integrin alpha4/VCAM-1 and LFA-1/ICAM-1 and -2.

Binding of T lymphocytes within the different compartments of the secondary lymphoid organs is crucial for the function of the cellular and the humoral immune response. It is still not known which adhesion molecules guide T cells to the distinct areas of the lymphoid microenvironment. In the current study an in situ adhesion assay was used to define the receptors for binding of T cells to human tonsils. The T cell lines Jurkat and MOLT-4 and normal, activated T cells were found to bind exclusively to germinal centers. Jurkat cells used the receptor pair integrin-alpha4 (VLA-4alpha)/VCAM-1, whereas activated MOLT-4 cells and normal T cells bound via both adhesion pathways, namely via integrin-alpha4/VCAM-1 and LFA-1/ICAM-1 and -2. It is suggested that these adhesion mechanisms are involved in the migration of T cells into the germinal centers of secondary lymphoid organs and that they influence the selection of B cells by apoptosis.

Antigens, CD↗

PubMed1994

The astrocyte inhibition of peripheral nerve regeneration is reversed by Schwann cells.

Schwann cell transplantation into the lesioned or demyelinated central nervous system (CNS) is being extensively explored as an approach to favorably influencing repair in the CNS. Under a variety of circumstances, however, the CNS glial microenvironment appears to offer an unfavorable terrain for the promotion of neurite elongation and for Schwann cell differentiation. Due to the heterogeneity of the cellular contents at injury sites, the specific role of each cell type present in limiting Schwann cell function is unclear. The damaged peripheral nervous system, a system capable of substantial regeneration (and free of the potentially negative influence of oligodendrocytes), represents a valuable model in which to specifically evaluate the influence of astrocytes on Schwann cell function. In the present study, purified cortical astrocyte populations were seeded into semipermeable guidance channels alone or in combination with adult Schwann cell populations to determine their effects on regeneration across an 8-mm gap in the transected sciatic nerve of the adult rat. Channels were prepared with (or without) a defined cellular content, implanted in inbred Lewis rats and evaluated after 3 weeks. Channels seeded with astrocytes alone impeded regeneration, regardless of the maturity of the astrocytes (7-8 days vs 28 days in culture) and their seeding density (40 vs 80 x 10(6) cells/ml). On the other hand, Schwann cells derived from adult sciatic nerve seeded at similar densities enhanced the regenerative process. Regenerative capacity was diminished when astrocytes were combined with Schwann cells; the rate of regeneration increased as the number of Schwann cells in the astrocyte/Schwann cell mixture increased. Immunostaining of the nerve stumps related to astrocyte-seeded channels and of the regenerated tissue in the astrocyte-Schwann cell-seeded channels indicated that astrocytes had migrated into the proximal nerve stump; only a few astrocytes remained within the regenerated cable. The present experiments show that although astrocytes alone inhibit nerve regeneration, Schwann cells are able to partially overcome this inhibition if they are provided in sufficient numbers. We believe these observations will be valuable in considering clinical strategies to use autologous Schwann cell transplantation to influence CNS regeneration.

Acrylonitrile↗

PubMed1988

Effects of B-aminopropionitrile on mineralization during endochondral ossification in chick tibia.

Two-week-old white leghorn chicks were fed a diet containing BAPN (0.05%) for three weeks. Thirty-six hours before sacrifice, the controls and BAPN fed chicks were dosed with 35S. The zone of provisional calcification was isolated, and 35S incorporation was estimated by liquid scintillation counting. Alkaline phosphatase and Ca+2-ATPase were biochemically analyzed. Microdensitometry, to assess the level of mineralization, was done on epiphysis and the metaphysis. Morphometry was performed on the various zones of growth plate. 35S incorporation was significantly lower in the bones of BAPN treated chicks as compared to the controls. The enzymatic studies showed a significant inhibition of alkaline phosphatase and Ca+2-ATPase. The microdensitometric studies showed a smaller area of highly mineralized bone in the zones of provisional calcification of the BAPN treated chicks as compared to the controls. Morphometry showed a reduction in the width of the zone of calcification in BAPN treated chicks as compared to the controls. On the basis of the above data, it is suggested that BAPN induced inhibition of mineralization during endochondral ossification may be the result of a lower synthesis of sulfur containing GAG's, the inhibition of enzymes alkaline phosphatase and Ca+2-ATPase and the derangement of cellular zones of the growth plate. The implications of these results lie in the fact that mineralization is dependent on multifactorial control of the microenvironment of bone and cartilage.

Alkaline Phosphatase↗

PubMed2001

Nitric oxide and inflammatory mediators in the perpetuation of osteoarthritis.

Articular chondrocyte production of nitric oxide (NO) and other inflammatory mediators, such as eicosanoids and cytokines, are increased in human osteoarthritis. The excessive production of nitric oxide inhibits matrix synthesis and promotes its degradation. Furthermore, by reacting with oxidants such as superoxide anion, nitric oxide promotes cellular injury and renders the chondrocyte susceptible to cytokine-induced apoptosis. PGE(2) exerts anabolic and catabolic effects on chondrocytes, depending on the microenvironment and physiologic condition. The increased expression of inducible NOS (iNOS) and cyclo-oxygenase-2 (COX-2) in OA chondrocytes is largely due to the increased expression of pro-inflammatory cytokines, particularly IL-1, which act in an autocrine/paracrine fashion to perpetuate a catabolic state that leads to progressive destruction of articular cartilage. The initiating factors for the production of inflammatory mediators include altered biomechanical forces; their continued production may be augmented by an increase in extracellular matrix proteins acting through ligation of surface integrins.

Cartilage, Articular↗

PubMed2005

Lymphotoxin-beta receptor signaling is required for the homeostatic control of HEV differentiation and function.

The lymphotoxin axis is important for the maintenance of several specialized lymphoid microenvironments in secondary lymphoid tissue. Lymphoid-tissue architecture is highly plastic and requires continual homeostatic signaling to maintain its basal functional state. The cellularity of lymph nodes in adult mice was reduced by systemic blockade of lymphotoxin-beta receptor (LTbeta R) signaling with a soluble decoy receptor both in resting and reactive settings. This reduction in cellularity resulted from greatly impaired lymphocyte entry into lymph nodes due to decreased levels of peripheral lymph node addressing (PNAd) and MAdCAM on high endothelial venules (HEV). LTbeta R signaling was required to maintain normal levels of RNA expression of MAdCAM, and also of PNAd by regulating the expression of key enzymes and scaffold proteins required for its assembly. Thus, the homeostatic maintenance of functional HEV status in adult mice relies largely on LTbeta R signaling.

Animals↗

PubMed2006

Role of Langerhans cells in cutaneous protective immunity: is the reappraisal necessary?

Langerhans cells (LC) are constantly exposed to external antigens and pathogens, and they are the cutaneous counterpart of dendritic cells (DC). DC not only act as professional antigen presenting cells to induce antigen-specific T cells for adaptive immune responses, but they also initiate a cascade of innate immune responses by sensing these danger signals. However, recent studies challenge the classical paradigm to position LC in the center of cutaneous immunity. Although LC express toll-like receptors (TLRs) that recognize bacterial and viral products, exposure to pathogen-associated TLR ligands triggers neither sufficient LC maturation nor good production of cytokines and chemokines. LC also lack the ability to produce IFN-gamma by any stimuli, and together with the characteristics of LC that are prone to produce Th2-type chemokines and to produce much less IL-12 in the presence of keratinocyte-derived GM-CSF, LC primarily may not have the character to induce Th1- and Tc1-type immune responses necessary for protective cellular immunity. Moreover, LC maturation is inhibited, rather than enhanced, by type I IFNs that are abundantly produced in viral infections in the skin microenvironment. Finally, recent data suggest that LC may not directly present viral antigens to T cells for their activation in mouse models of cutaneous viral infection. The alternative player in protective immune responses may be surrounding keratinocytes, which may modulate LC functions indirectly. Dermal DC may also participate in this scheme. Further studies are required to clarify the role of LC in their interplay with keratinocytes and other DC subsets, and to draw the entire picture of the cutaneous immune system against pathogens.

Animals↗

PubMed1982

Thymocyte precursors in early-thymectomized Xenopus: migration into and differentiation in allogenic thymus grafts.

In an anuran amphibian, Xenopus laevis, thymectomy of 4-day-old larvae abrogates T-cell dependent immune responsiveness. When such early-thymectomized (TX) diploid frogs were implanted with histocompatible triploid thymuses and grafted 8 weeks later with skin from third-party donors, the grafts were rejected relatively normally in 20-27 days. Microspectrophotometric determination of ploidy 3-5 months after thymus reconstitution revealed that most thymocytes were donor-derived. In contrast, when TX frogs received allogeneic triploid thymuses, they rejected skin grafts from a third-party donor relatively slowly (48-92 days) but did not reject skin from the thymus donor. Most thymocytes in such animals were of host origin. Host thymocytes were present 4 weeks after thymus implantation and became dominant population by 12 weeks. Few thymus implant-derived donor cells were detectable in the host spleen. These data suggest that existence of precursor cells in TX Xenopus that can functionally differentiate along a T-cell pathway as a result of microenvironment provided by the thymus implant.

Animals↗

PubMed2007

Beyond tumorigenesis: cancer stem cells in metastasis.

The importance of cancer stem cells (CSCs) in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression, particularly with respect to metastasis, has not been well-defined. Cancer metastasis requires the seeding and successful colonization of specialized CSCs at distant organs. The biology of normal stem cells and CSCs share remarkable similarities and may have important implications when applied to the study of cancer metastasis. Furthermore, overlapping sets of molecules and pathways have recently been identified to regulate both stem cell migration and cancer metastasis. These molecules constitute a complex network of cellular interactions that facilitate both the initiation of the pre-metastasis niche by the primary tumor and the formation of a nurturing organ microenvironment for migrating CSCs. In this review, we surveyed the recent advances in this dynamic field and propose a unified model of cancer progression in which CSCs assume a central role in both tumorigenesis and metastasis. Better understanding of CSCs as a fundamental component of the metastatic cascade will lead to novel therapeutic strategies against metastatic cancer.

Animals↗