Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “multicellularity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1992

[A new method of in vitro chemosensitivity test using multicellular spheroids of cholangiocarcinoma cell line cocultured with fibroblasts].

We applied the multicellular spheroids which consist of cholangiocarcinoma cell line (MEC) and human dermal fibroblasts (HDF) to in vitro chemosensitivity test. Five-day multicellular spheroids were incubated with 1.5 micrograms/ml of mitomycin C (MMC) for 24 hrs. Then, cell kinetics of MEC and HDF in a spheroid was determined by flow cytometric analysis. Twenty four hrs after treatment with MMC, both MEC and HDF were accumulated on S phase. Seven-day after treatment, DNA histogram in MEC returned to normal, but that of HDF was disappeared. These results showed that the multicellular assay could be more like on in vivo like chemosensitivity test.

Adenocarcinoma↗
PubMed1991

Bacterial swarming: an example of prokaryotic differentiation and multicellular behaviour.

Bacterial swarming involves the differentiation of vegetative cells into hyperflagellated swarm cells which undergo cycles of rapid and coordinated population migration across solid surfaces. Species capable of this simple form of developmental behaviour lie on the boundary between unicellular and multicellular organisms and provide processes for study which are not only of intrinsic interest but which are analogous to components of more complex eukaryotic systems. This review attempts to place current knowledge of bacterial swarming within the framework provided by more extensively studied forms of prokaryotic multicellular behaviour. It discusses the potential of swarming as a readily accessible model of differentiation and multicellular behaviour and describes evidence indicating that swarming differentiation plays an important role in bacterial virulence.

Bacterial Adhesion↗
PubMed1991

Differentiation and maturation of macrophages into interdigitating cells and their multicellular complex formation in the fetal and postnatal rat thymus.

Three mouse anti-rat macrophage monoclonal antibodies, TRPM-1, TRPM-2, and TRPM-3, as well as anti-rat Ia monoclonal antibody, were used to study the emergence, differentiation, and maturation of macrophages in the fetal and postnatal rat thymus immunohistochemically and immunoelectron microscopically. At 14 days of gestation, primitive/fetal macrophages entered the thymic primordium and showed Ia expression, where afterwards the epithelial cells also expressed Ia antigens prominently at 15 days of gestation. After 16 days of gestation, differentiation of a subpopulation of primitive/fetal macrophages into interdigitating cells (IDCs) is suggested. From 19 days of gestation, TRPM-1-positive dendritic cells including IDCs started forming multicellular complexes with thymocytes and the epithelial cells also formed similar complexes with thymocytes. One day after birth, TRPM-1 positive IDC-thymocyte complexes distributed throughout the thymic medulla. The number of TRPM-1- and Ia-positive IDCs increased by day, and Langerhans cells (LCs) appeared in the thymic medulla within a few days after birth. By two weeks after birth, the distribution pattern of Ia- and TRPM-1-positive cells became similar to that of adult rats. In ontogeny, intimate cell membrane appositions were frequently observed between thymocytes and Ia-positive epithelial cells or IDCs in the thymic multicellular complexes. These complexes were discriminated into two types; epithelial cell-thymocyte complexes and IDC- or LC-thymocyte ones. In vitro, two types of the thymic nurse cells (TNCs) were identified: epithelial cells and IDCs or LCs. Besides epithelial cells, IDCs or macrophages formed rosettes with thymocytes. These TNCs and rosettes in vitro seem to correspond to the thymic multicellular complexes in vivo.

Animals↗
PubMed1983

Growth of mammalian multicellular tumor spheroids.

The in vitro growth of small (0.05 to 3 mm diameter) avascular multicellular tumor spheroids from six rodent and two human tumor lines has been analyzed. Surprisingly, the radial increase of multicellular tumor spheroids is linear with time after a brief initial period of geometric growth. These multicellular tumor spheroids are shown to have a constant thickness of proliferative outer crust and of middle nonproliferative but viable mantle. An analytical model for their growth is developed which explains the growth pattern. This constant crust thickness model leads to a progressively diminishing growth fraction as radius increases and should be applicable to such early growth of micrometastases in vivo. The model also provides a procedure for determining cell cycle time.

Animals↗
PubMed1982

Probable clonal origin of aldosteronomas versus multicellular origin of parathyroid "adenomas".

Adrenocortical adenomas causing hyperaldosteronism in two women heterozygous at the X chromosome-linked glucose-6-phosphate dehydrogenase (G-6-PD) locus exhibited only one G-6-PD isoenzyme. This finding suggests a clonal development for these benign tumors and contrasts with the multicellular origin of parathyroid adenomas reported in three patients from our institution in 1977 and found subsequently in seven other hyperparathyroid women whose cases are reported here. One of these seven patients had hereditary hyperparathyroidism. In this case each of three glands removed showed both A and B G-6-PD isoenzymes in similar ratios as were found in normal tissues. The multicellular origin of hereditary hyperparathyroidism is compatible with the concept of parathyroid lesions being manifestations of the first genetic event in Knudson's two-mutational-event theory for the initiation of cancer. The multicellular origin of sporadic parathyroid tumors suggest that they are caused by some factors stimulating many cells in the parathyroid glands. The young average age of onset of eight cases of parathyroid cancer from five families with hereditary hyperparathyroidism in the literature is also compatible with Knudson's theory. G-6-PD studies of other aldosteronomas, parathyroid tumors, and other endocrine neoplasms may provide important information about the pathogenesis of these conditions.

Adenoma↗
PubMedDate not supplied

Impact of multicellular resistance on the survival of solid tumors, including micrometastases.

One of the reasons for the development of cancers and their relentless malignant progression--even in the face of highly toxic anticancer therapies--is an enhanced ability to bypass mechanisms responsible for precipitating cell death. The latter include active cell death mechanisms often referred to as programmed cell death or apoptosis. Active cell death is a genetically controlled, intrinsic suicide process, and evidence is rapidly accumulating that cancers are more resistant to undergoing apoptosis than normal cells. This may be a major factor explaining the ability of small numbers of tumor cells, e.g. tumor emboli, to survive transit in the bloodstream and form distant metastases in ectopic organ sites. In addition, because many therapeutic agents ultimately kill tumor cells by inducing apoptosis, acquisition of an apoptosis-resistant phenotype could be a generic mechanism of drug or radiation resistance in cancer patients. It follows that uncovering the basis of the enhanced survival capacity of tumor cells is fundamental to gaining a better understanding of tumor progression, metastasis formation, and response to therapy. In this respect many of the principles thought to regulate apoptosis in cancers have been established using conventional, two-dimensional monolayer cell cultures of 'liquid' tumors, i.e. unicellular model systems. Suppression of apoptosis in solid tumors, however, may be governed by different cellular and genetic mechanisms. Evidence is presented in support of this hypothesis, and that multicellular architecture may render individual tumor cells within solid tumors less susceptible to apoptosis. This multicellular resistance--which may represent a form of group protection--can also be induced or acquired during cytotoxic drug chemotherapy or cytokine-mediated growth inhibition of solid tumors. It follows that disruption of solid tumor multicellularity may provide a means of enhancing the therapeutic destruction of small solid tumors such as occult micrometastases. Such disruptions may be brought about by a variety of so-called antiadhesive agents.

Animals↗
PubMed1993

An experimental model of acute liver injury using multicellular spheroids composed of rat parenchymal and non-parenchymal liver cells.

Massive hepatic cell necrosis can be induced by Corynebacterium parvum and lipopolysaccharide (LPS) in rats. In this model, serum LDH, GOT and GPT activities are significantly increased in vivo within several hours after LPS injection. An in vitro experimental acute liver injury animal model was produced by using multicellular spheroids composed of rat parenchymal and non-parenchymal liver cells. These multicellular spheroids were prepared by detaching the confluent monolayer on the collagen-conjugated thermo-responsive polymer coated culture dish at a temperature below the lower critical solution temperature and culturing it on the non-adhesive substratum. LPS caused clear elevations of GOT, GPT and LDH activities from these spheroids into the medium. However, the increase of LDH activity was only observed in the monolayer culture system. These results suggest that the multicellular spheroids of liver cells are useful models as an alternative to animal tests for hepatotoxicity.

Alanine Transaminase↗
PubMed1995

[Hormone-mediated calcium responses of rat and human hepatocytes. Study of multicellular systems by videomicroscopy].

OBJECTIVES AND METHODS: Activation of hepatocyte hormonal receptors leads to the mobilization of intracellular Ca2+ which is thought to be an elaborate system for encoding hormonal messages. We studied hormone-induced calcium signals in freshly isolated multicellular systems of normal rat and human hepatocytes. Calcium signals were recorded by videomicroscopy after stimulation with noradrenaline, angiotensin II, and vasopressin. RESULTS: Calcium signals were highly organized in multiplets: the different hepatocytes responded to Ca(2+)-mobilizing hormones in a sequentially ordered manner, with a first, a second (doublets) and a third (triplets) responding cells. This pattern was an intrinsic feature of the multicellular systems, and seemed to be a result of a gradual heterogeneity of the sensitivity of the different cells, to the hormones. The stimulation of the same multiplet with two different agonists and the removal of the hormone during cell responses provides some evidence for the major role of hormonal receptors in this heterogeneity. CONCLUSIONS: Hormone responses in multicellular systems of rat and human hepatocytes are highly elaborate. The density of hormonal receptors could be the major determinant of the sequential pattern of Ca2+ responses. Hormonal receptors may be gradually distributed among the different cells of the multiplets in vitro and along the porto-centrilobular axis in situ.

Angiotensin II↗
PubMedDate not supplied

[Ultrastructural organization of trichomes of a new group of multicellular gram-negative bacteria].

Peculiar trichome multicellular gram-negative bacteria were found in several types of soil, and were isolated as pure cultures. The bacteria are characterized by the following properties: (a) the presence of large regions of the periplasm, 200-300 nm thick, in the cells, the volume of the periplasm being greater than that of the cytoplasm; (b) a peculiar structure of multicellular trichomes in which the cells are surrounded by a common cell wall and a common periplasmic space; (c) a specific structure of trichome septa formed by membrane leaves and including no material of the cell wall; (d) the ability of protoplasts to divide within the trichome cell wall; (e) the ability to grow under anaerobic conditions. Therefore, these organisms belong to a new group of trichome multicellular bacteria.

Cell Membrane↗
PubMed1998

Multicellular resistance: another mechanism for multidrug resistance?

Cells cultured as spheroids present an heterogeneity similar to that of tumours in vivo. In the spheroid peripheral layers, cells are proliferating, deeper cells are non-cycling, when in the aggregate centre, cells form often a necrotic core. A multicellular resistance appears in spheroids, it is a result of the cell contact to other cells (homogeneous or heterogeneous cells) and/or to the extracellular matrix. The mechanism of this resistance is not known, nevertheless, it can be hypothesised to be linked to the spheroid centre hypoxia, to the quiescence of a large fraction of the cell population and to the apoptose inhibition due to the cell contact. The classical or unicellular mechanisms of resistance, as mdr1, MRP, can coexist with the multicellular resistance, but are not responsible for this resistance. The spheroid model of culture is a good opportunity to study a resistance type which looks close to the tumour resistance found in vivo in mice and in patients. A new class of therapeutic molecules appears that can reverse this multicellular resistance, inhibit tumours growth and preclude metastases. The principal mechanism of action of this new pharmacological class appears to be the disruption of the intercellular adhesion forces. Preliminary results obtained with these compounds in patients are promising.

Journal Article↗
PubMed1998

[Multicellular resistance: another mechanisms of pleiotropic resistance?].

Cells cultured as spheroids present an heterogeneity similar to that of tumours in vivo. In the spheroid peripheral layers, cells are proliferating, deeper cells are non-cycling, when in the aggregate centre, cells from often a necrotic core. A multicellular resistance appears in spheroids, it is a result of the cell contact to other cells (homogeneous or heterogeneous cells) and/or to the extracellular matrix. The mechanism of this resistance is not known, nevertheless, it can be hypothesised to be linked to the spheroid centre hypoxia, to the quiescence of a large fraction of the cell population and to the apoptosis inhibition due to the cell contact. The "classical" or "unicellular" mechanisms of resistance, as mdr1, MRP, can coexist with the multicellular resistance, but are not responsible for this resistance. The spheroid model of culture is a good opportunity to study a resistance type which looks close to the tumour resistance found in vivo in mice and in patients. A new class of therapeutic molecules appears that can reverse this multicellular resistance, inhibit tumours growth and preclude metastases. The principal mechanism of action of this new pharmacological class appears to be the disruption of the intercellular adhesion forces. Preliminary results obtained with these compounds in patients are promising.

Cell Cycle↗
PubMed1999

Molecular self-recognition and adhesion via proteoglycan to proteoglycan interactions as a pathway to multicellularity: atomic force microscopy and color coded bead measurements in sponges.

During the emergence of multicellular organisms, molecular mechanisms evolved to allow maintenance of anatomical integrity and self-recognition. We propose that carbohydrates from proteoglycans, as the most peripheral cell surface, and matrix molecules might have provided these key adhesion and recognition functions. If so, the Porifera as the simplest metazoans alive today should retain, at least in part, proteoglycan adhesion and recognition mechanisms. Early work on cell adhesion of dissociated marine sponge cells provided important phenomenological evidence for cell sorting. Here is reviewed recent work on molecular mechanisms of cell recognition and adhesion mediated by cell surface proteoglycans purified from three marine sponge species, Microciona prolifera, Halichondria panicea, and Cliona celata. Biochemical characterization of isolated proteoglycans showed that each species expressed a unique type of primordial molecule named glyconectins. These proteoglycans displayed species-specific self-recognition and adhesion in color-coded bead, cell, and blotting assays. The specificity of homophilic proteoglycan to proteoglycan interactions in the Porifera approaches the binding selectivity of the evolutionarily advanced immunoglobulin superfamily system. Such xeno-selectivity may be a new paradigm for the molecular self-recognition, which was a fundamental requirement in the self/non-self discrimination during the emergence of multicellularity and further divergence of species. We have used atomic force microscopy (AFM) technology to directly measure intermolecular binding strength between individual pairs of ligand and receptor molecules in physiological solution. Homophilic glyconectin interactions were investigated by AFM after covalent attachment of the protein core to the sensor tip and to a flat surface, leaving the carbohydrates unmodified. AFM measurements of the binding strength between glyconectins indicated that one pair of molecules could theoretically hold the weight of 1,600 cells in physiological solution. These results provided the first essential and quantitative evidence that proteoglycan-proteoglycan binding can perform the adhesion function that we have assigned to it. Our investigations with purified proteoglycans from the marine sponge M. prolifera (glyconectin 1) using bead and cell adhesion assays have provided evidence that a new molecular mechanism of polyvalent and specific glycan-glycan binding between proteoglycans can mediate cell recognition and adhesion. Partial sequencing of the glycans has revealed two new cell adhesion carbohydrate structures: (3)GlcNAc(3OSO3)beta1-3Fuc and Pyr4,6Galbeta1-4GlcNAcbeta1-3Fuc.

Animals↗
PubMed1998

Hypotonic Ca2+ signaling and volume regulation in proliferating and quiescent cells from multicellular spheroids.

Hypotonicity-induced Ca2+ signals and volume regulation were studied in proliferating and quiescent subpopulations of multicellular prostate cancer spheroids. Enzymatic dissociation of multicellular spheroids 100+/-19 microm in diameter, which are entirely proliferative, yielded a population of cells with a mean cell diameter of 17.5+/-1.4 microm. After dissociation of spheroids in a size class of 200+/-30, 300+/-60, and 400+/-65 microm in diameter, two subpopulations of cells with mean cell diameters corresponding to 12.9+/-1.9 microm and 16.7+/-2 microm were discriminated. The subpopulation of large cells was shown to be proliferative by positive Ki-67 antibody staining; the subpopulation of small cells was Ki-67 negative, indicating cell quiescence. In a spheroid size class of 100+/-19 microm, a distinct subpopulation of quiescent cells was absent. Superfusion by hypotonic solutions revealed that only the proliferating cell fraction showed a regulatory volume decrease (RVD) and a [Ca2+]i transient. Both effects were absent in the quiescent cell population. The [Ca2+]i transient persisted in low (10 nM) Ca2+ solution and in the presence of 4 mM extracellular Ni2+ but was abolished in the presence of the endoplasmic reticulum Ca2+-ATPase blocker 2,5-di-tert-butyl-hydrochinone (t-BHQ). The t-BHQ likewise inhibited RVD, indicating that Ca2+ release from intracellular stores was necessary for RVD. Moreover, [Ca2+]i and RVD were dependent on an intact microfilament cytoskeleton because after 30 min of preincubation with cytochalasin B the [Ca2+]i transient was significantly reduced and RVD was abolished. The absence of RVD and [Ca2+]i transient in quiescent cells may be due to differences in the amount and the cytosolic arrangement of F-actin observed in quiescent cells.

Actins↗
PubMed2000

Conserved mechanisms of repair: from damaged single cells to wounds in multicellular tissues.

The capacities to repair minor membrane holes in damaged single cells, and the more major damage sustained when a multicellular tissue is wounded, both involve a series of ancient and highly conserved processes. In this review, we discuss what is known about how the plasma membrane of a single cell and its underlying cortical cytoplasm are repaired following cell damage, and how multicellular wounds to the embryonic and adult skin are also able to heal. Pivotal for all these processes is the actin cytoskeleton and we draw analogies between the actin machineries that drive repair and those that appear to underlie several genetically tractable morphogenetic processes that occur during Drosophila and Caenorhabditis elegans embryogenesis.

Actins↗
PubMed1985

Multicellular tumor spheroid interactions with bone cells and bone.

In vitro coculture techniques were used to study HSDM1C1 murine fibrosarcoma multicellular tumor spheroid (HSDM1C1-MTS) interactions with mouse calvarial bone cells having osteoblastic characteristics and mouse bone explants. HSDM1C1-MTS attached to confluent bone cell monolayers and their attachment rate was quantified. HSDM1C1-MTS interaction with bone cells was further demonstrated by the release of 3H-deoxyuridine from prelabeled bone cells during coculture with multicellular tumor spheroids. HSDM1C1-MTS-induced cytotoxicity was mimicked by the addition of 10(-5) M prostaglandin E2 (PGE2) to 3H-deoxyuridine-labeled bone cells. The effects of low (10(-9) M) and high (10(-5) M) concentrations of PGE2 on bone cell proliferation were also studied. Higher concentrations of PGE2 inhibited bone cell proliferation. HSDM1C1-MTS resorbed living explants in the presence of indomethacin, suggesting that other tumor cell products may also participate in bone resorption. HSDM1C1-MTS caused direct bone resorption as measured by the significantly elevated release of 45Ca from prelabeled, devitalized calvaria. However, the growth of a confluent bone cell layer on devitalized, 45Ca-prelabeled calvaria resulted in a significant reduction in the amount of 45Ca released subsequent to the seeding of HSDM1C1-MTS onto the explants. Bone cells at the bone surface may act as a barrier against invasion and tumor cell-mediated bone resorption. Violation of this cellular barrier is achieved, in part, by tumor cell products.

Animals↗
PubMed1995

Multicellular-vesicle-promoting polypeptide from Trichoplusia ni: tissue distribution and N-terminal sequence.

An N-terminal amino acid sequence of a 16.9 kDa hemolymph polypeptide, "Vesicle Promoting Factor" (VPF) from Trichoplusia ni, revealed a high sequence homology (70%) with Manduca sexta apolipophorin-III. A polyclonal antibody developed against VPF, however, was not immunoreactive with either purified M. sexta or T. ni apolipophorin-III. Immunoblots of tissue homogenates of T. ni indicated that VPF was present in imaginal wing discs, central nervous system (CNS), silk glands, midgut and hemocytes from fifth instar larvae, and also in the IAL-TND1 cell line which can grow as either fluid-filled multicellular vesicles or multicellular aggregates. VPF was also detected immunologically in the hemolymph of adults of T. ni, and in hemolymph of adults and larvae of Galleria mellonella and Heliothis virescens. Testes, midgut, hemocytes, and wing discs, but not Malpighian tubules, of T. ni released VPF into tissue culture medium during a 3 h incubation period.

Amino Acid Sequence↗
PubMed2006

Individual cell-based models of the spatial-temporal organization of multicellular systems--achievements and limitations.

Computational approaches of multicellular assemblies have reached a stage where they may contribute to unveil the processes that underlie the organization of tissues and multicellular aggregates. In this article, we briefly review and present some new results on a number of 3D lattice free individual cell-based mathematical models of epithelial cell populations. The models we consider here are parameterized by bio-physical and cell-biological quantities on the level of an individual cell. Eventually, they aim at predicting the dynamics of the biological processes on the tissue level. We focus on a number of systems, the growth of cell populations in vitro, and the spatial-temporal organization of regenerative tissues. For selected examples we compare different model approaches and show that the qualitative results are robust with respect to many model details. Hence, for the qualitative features and largely for the quantitative features many model details do not matter as long as characteristic biological features and mechanisms are correctly represented. For a quantitative prediction, the control of the bio-physical and cell-biological parameters on the molecular scale has to be known. At this point, slide-based cytometry may contribute. It permits to track the fate of cells and other tissue subunits in time and validated the organization processes predicted by the mathematical models.

Animals↗
PubMed1989

Effect of polarity and differentiation on antibody localization in multicellular tumour spheroid and xenograft models and its potential importance for in vivo immunotargeting.

Two monoclonal antibodies (MAbs) AUAI and HMFGI recognize antigens located on different membrane domains of polarized epithelial cells. We have assessed the accessibility of these antigens in multicellular tumour spheroids produced in culture using a well-polarized (HRA-19) and a non-polarized cell line (LoVo) of human large-bowel carcinoma origin. Multicellular spheroids of HRA-19 cells develop polarity, so that the membrane which is in contact with the culture medium (apical) becomes antigenically distinct from the membrane facing the centre of the spheroids (basolateral). This was confirmed by immunostaining sections of spheroids with 2 MAbs, AUAI and HMFGI. AUAI recognizes an antigen located exclusively on the basolateral membranes of polarized epithelial cells, and stained only internal membranes in spheroid sections. Conversely HMFGI, which recognizes an antigen located on the apical membranes, stained only the periphery of the spheroids. These 2MAbs were then radiolabelled with 125I and incubated with live spheroids for 4 hr at 37 degrees C. Autoradiographs of spheroid sections showed a marked difference between the 2 MAbs. 125I-HMFGI-radioantibody localized exclusively on the spheroid surface in a pattern identical to the in vitro immunostaining pattern, while 125I-AUAI radioantibody showed no binding in spite of the uniform presence of antigen on all tumour cells basolaterally. This appeared to be the result of the inaccessibility of basolateral antigenic sites in well-polarized epithelial cells because of the tight junctions connecting these cells at their apical surfaces. In contrast to the HRA-19 cell line LoVo, spheroids do not develop polarity; as a result, when stained with AUAI, variable antigenic expression all over the cell surface was seen. Autoradiographs of these spheroids showed 125I-AUAI binding with a penetration to a depth of about 1-3 cells, while HMFGI which shows no reactivity with this cell line in vitro, did not bind. This phenomenon was further investigated in xenografts of the HRA-19 cell line. It was shown that in a well-differentiated adenocarcinoma where the tumour cells forming acini are arranged in a polarized fashion, the luminal antigenic sites may be inaccessible to the injected MAb. The striking differences in binding of MAbs on polarized and unpolarized tumours indicate the importance of cell polarization and exact location of antigenic sites for in vivo immunotargeting.

Adenocarcinoma↗