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At least 361 records · Page 20Linked to original sources
PubMed1994

Less initial rejoining of X-ray-induced DNA double-strand breaks in cells of a small cell (U-1285) compared to a large cell (U-1810) lung carcinoma cell line.

Cells of a small cell lung carcinoma cell line, U-1285, and an undifferentiated large cell lung carcinoma cell line, U-1810, differ in radiosensitivity in parallel to the clinical radiosensitivity of the kind of tumors from which they are derived. The surviving fraction at 2 Gy (SF2) was 0.25 that of U-1285 cells and 0.88 that of U-1810 cells. We investigated the induction of DNA double-strand breaks (DSBs) by X rays and DSB rejoining in these cell lines. To estimate the number of DSBs we used a model adapted for pulsed-field gel electrophoresis (PFGE). The induction levels were of the same magnitude (0.46 and 0.51 DSB/100 Mbp/Gy for U-1810 and U-1285 cells, respectively). These levels of induction do not correlate with radiosensitivity as measured by cell survival assays. Rejoining of DSBs after doses in the range of 0-50 Gy was followed for 0, 15, 30, 60 and 120 min. We found a difference in the velocity of repair during the first hour after irradiation which is parallel to the differences in radiosensitivity. Thus U-1810 cells exhibit a fast component of repair, with about half of the DSBs being rejoined during the first 15 min, whereas U-1285 cells lack such a fast component, with only about 5% of the DSBs being rejoined after the same time. In addition there was a numerical albeit not statistical difference at 120 min, with more residual DSBs in the U-1285 cells compared to the U-1810 cells.

Carcinoma, Large Cell↗
PubMed1999

Human non-germinal center B cell interleukin (IL)-12 production is primarily regulated by T cell signals CD40 ligand, interferon gamma, and IL-10: role of B cells in the maintenance of T cell responses.

Interleukin (IL)-12 is expressed mainly in antigen-presenting cells after challenge with microbial material or after CD40 activation. Although IL-12 was cloned from human Epstein-Barr virus (EBV)-transformed B cell lines, surprisingly, CD40 ligation on murine B cells did not lead to IL-12 production, suggesting that murine B cells do not produce IL-12. Here we demonstrate that a subset of human tonsillar B cells can be induced to express and secrete bioactive IL-12. The major stimulus to produce IL-12 in human B cells was CD40 ligation. In contrast, B cell receptor cross-linking did not induce IL-12. Expression of IL-12 after CD40 activation was restricted to CD38(-)IgD+/- non-germinal center (non-GC) B cells. CD40 ligation and interferon (IFN)-gamma exhibited synergistic effects on IL-12 production, whereas IL-10 abrogated and IL-4 significantly inhibited IL-12 production by these B cells. In contrast to IL-12, production of IL-6 is conversely regulated, leading to significant increase after CD40 ligation in the presence of the T helper type 2 (Th2) cytokine IL-4. Cord blood T cells skewed towards either a Th1 or a Th2 phenotype maintained their cytokine expression pattern when restimulated with allogeneic resting B cells. Blockade of CD40 and/or IL-12 during T-B interaction significantly reduced IFN-gamma production by the T cells. This suggests a model whereby B cells produce either IL-12 or IL-6 after contact with T cells previously differentiated towards Th1 or Th2. Furthermore, IL-12 and IL-6 might provide a positive feedback during cognate T-B interactions, thereby maintaining T cells' differentiation pattern during amplification of the immune response.

Antigen-Presenting Cells↗
PubMed1999

Cloning thymic precursor cells: demonstration that individual pro-T1 cells have dual T-NK potential and individual pro-T2 cells have dual alphabeta-gammadelta T cell potential.

Thymic progenitors have the capacity to generate alphabeta T cells, gammadelta T cells, and NK cells. To determine whether these three lineages derive from a single precursor cell or from different precursors, a procedure was developed for cloning precursor cells from mouse embryonic thymus. The progeny of each pro-T cell clone were then tested for the potential to generate alphabeta, gammadelta, and NK cells. Of these precursor clones, about half displayed dual potential, developing into either T cells or NK cells, demonstrating the existence of a common T/NK precursor cell in the thymus. The other half of the clones were restricted to T cell development. No precursor clones were restricted to NK development. The common T/NK precursors were shown to be of the pro-T1 (CD25(-)) stage whereas the T-restricted precursors were shown to be of the later pro-T2 (CD25(+)) stage. Both alphabeta and gammadelta T cells were generated from all clones derived from either pro-T1 or -T2 precursors. This shows that commitment of a cell to the alphabeta versus gammadelta lineages does not precede rearrangement of the TCR genes (which occurs immediately after the pro-T2 stage).

Animals↗
PubMed1987

Differentiation of B cell progenitors in vitro: generation of surface IgM+ B cells, including Ly-1 B cells, from Thy-1- asialoGM1+ cells in newborn liver.

We have established a stromal adherent cell line (ST2) from fetal liver that promotes growth and differentiation of early B lineage cells. Many cells in the "null population" (3-5%) from newborn liver that lack antigens found on mature erythroid, myeloid or lymphoid cells proliferate extensively on this ST2 layer. Further division of this cell fraction on the basis of Thy-1 and asialoGM1 (aGM1) expression discriminates cells that predominantly proliferate from those that differentiate on the ST2 layer. Among four populations, Thy-1+ aGM1- cells proliferate most but yield few B220+ cells. In contrast, Thy-1- aGM1+ cells proliferate to a very limited extent, but most (greater than 90%) start to express B220 and a large fraction (up to 50%) become surface IgM+ after 2 weeks of culture. These B cells include cells expressing the pan-T cell molecule Ly-1, that is, Ly-1 B cells. Curiously, this Thy-1- aGM1+ cell population is largely absent from bone marrow in adult mice.

Animals↗
PubMed1999

Linker for activation of T cells (LAT), a novel immunohistochemical marker for T cells, NK cells, mast cells, and megakaryocytes: evaluation in normal and pathological conditions.

LAT (linker for activation of T cells) is an integral membrane protein of 36-38 kd that plays an important role in T cell activation. Using a rabbit polyclonal antibody generated against the cytosolic portion of LAT, we investigated the immunohistochemical expression of LAT in normal and pathological hematolymphoid tissues. LAT reacts with human T cells in paraffin sections, including decalcified bone marrow trephines. LAT appears early in T cells at the thymocyte stage and before TdT expression in embryos, and is expressed in peripheral lymphoid tissues, without restriction to any T cell subpopulations. In addition to T cells, natural killer (NK) cells (evaluated with flow cytometry), megakaryocytes and mast cells are also LAT-positive, whereas B cells and other myeloid and monocytic derived cells are negative. Tested on a total of 264 paraffin-embedded tissue biopsies, LAT reacted with the great majority (96.8%) of T/NK-cell neoplasms, covering the full range of T cell maturation. Although antibodies to both LAT and CD3 had a similarly high sensitivity in the staining of T/NK-cell lymphomas, when used in conjunction, they successfully identified a higher number of cases (98.4%). Atypical megakaryocytes from different hematological disorders, as well as mast cells in mastocytosis were also LAT-positive, but all neoplasms of B cell origin, Hodgkin's lymphomas, and several nonlymphoid malignancies were negative. These data indicate that the anti-LAT antibody may be of value to diagnostic histopathologists for the identification of T cell neoplasms.

Adaptor Proteins, Signal Transducing↗
PubMed1999

N-cadherin expressed on malignant T cell lymphoma cells is functional, and promotes heterotypic adhesion between the lymphoma cells and mesenchymal cells expressing N-cadherin.

Cadherins are Ca2+-dependent cell-cell adhesion molecules, and are involved in the formation and maintenance of the organocellular architecture. Using a combination of molecular biologic and biochemical methods, we analyzed cadherins expressed on cultured human malignant lymphoma cell lines (adult T cell lymphomas, human T cell leukemia virus type 1-negative T cell lines, and thymus-derived lymphoma cell lines), and obtained evidence that N-cadherin is the major cadherin expressed on these cells. These cells were found to form cell aggregates in a Ca2+-dependent manner, and more importantly to coaggregate and adhere with cells expressing N-cadherin, suggesting that N-cadherin on lymphoma cells is functionally active. Therefore, N-cadherin expressed on lymphoma cells could underlie the frequent invasion of these cells into the mesenchymal tissue in the skin and the central nervous system.

Cadherins↗
PubMed1998

Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase.

We previously demonstrated that both Tiam1, an activator of Rac, and constitutively active V12Rac promote E-cadherin-mediated cell-cell adhesion in epithelial Madin Darby canine kidney (MDCK) cells. Moreover, Tiam1 and V12Rac inhibit invasion of Ras-transformed, fibroblastoid MDCK-f3 cells by restoring E-cadherin-mediated cell-cell adhesion. Here we show that the Tiam1/Rac-induced cellular response is dependent on the cell substrate. On fibronectin and laminin 1, Tiam1/Rac signaling inhibits migration of MDCK-f3 cells by restoring E-cadherin-mediated cell- cell adhesion. On different collagens, however, expression of Tiam1 and V12Rac promotes motile behavior, under conditions that prevent formation of E-cadherin adhesions. In nonmotile cells, Tiam1 is present in adherens junctions, whereas Tiam1 localizes to lamellae of migrating cells. The level of Rac activation by Tiam1, as determined by binding to a glutathione-S-transferase- PAK protein, is similar on fibronectin or collagen I, suggesting that rather the localization of the Tiam1/Rac signaling complex determines the substrate-dependent cellular responses. Rac activation by Tiam1 requires PI3-kinase activity. Moreover, Tiam1- but not V12Rac-induced migration as well as E-cadherin-mediated cell- cell adhesion are dependent on PI3-kinase, indicating that PI3-kinase acts upstream of Tiam1 and Rac.

Animals↗
PubMed1980

Analysis of rat hemopoietic cells on the fluorescence-activated cell sorter. I. Isolation of pluripotent hemopoietic stem cells and granulocyte-macrophage progenitor cells.

A scheme is presented whereby pluripotent hemopoietic stem cells (PHSC) from rat bone marrow can be enriched 320-fold with the aid of the fluorescence- activated cell sorter. This scheme is based on the observations that PHSC are strongly positive for Thy-1 antigen (upper 10th percentile); have light- scattering properties (size distribution) between those of bone marrow lymphocytes and myeloid progenitor cells; and are relatively resistant to cortisone. It is estimated that PHSC may constitute 80 percent of the cells isolated according to these parameters. Candidate PHSC are described at the light and electron microscopic levels. At least two populations of accessory cells appear to influence the number and/or the nature of the hemopoietic colonies that form in the in vivo spleen colony-forming unit assay. Putative amplifier cells are strongly Thy-1(+) and cortisone sensitive; putative suppressor cells are weakly Thy-1(+) and cortisone resistant. Three subsets of granulocyte (G) -macrophage (M) progenitor cells (in vitro colony-forming cells [CFC]) are identified on the basis of relative fluorescence intensity for Thy-1 antigen: G-CFC are strongly Thy-l(+); M-CFC are weakly Thy-l(+); and cells that produce mixed G and M CFC have intermediate levels of Thy-1. GM-cluster-forming cells and mature G and M are Thy-1(-). The results suggest that G-CFC are bipotential cells that give rise to G and M-CFC; and that the latter produce mature M through a cluster- forming cell intermediate. Thy-1 antigen is also demonstrated on members of the eosinophil, megakaryocyte, erythrocyte, and lymphocyte cell series in rat bone marrow. In each instance, the relative concentration of Thy-1 antigen is inversely related to the state of cellular differentiation.

Animals↗
PubMed2003

T cell accumulation in B cell follicles is regulated by dendritic cells and is independent of B cell activation.

We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40(+) DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L-huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.

Animals↗
PubMed2005

Stromal cells attract B-cell progenitors to promote B-cell-B-cell contact and maturation.

The in vitro differentiation of B-lineage progenitors into Ig-secreting mature B cells has classically required a co-culture system containing lipopolysaccharide (LPS) and stromal cells. We have previously showed that B-lineage progenitors cultured in round-bottomed wells can mature and secrete immunoglobulin M (IgM) on par with cultures containing stromal cells. This clearly demonstrates that any factors essential for progenitor cell maturation can be found in cultures containing media, serum, LPS and B-cell progenitors. However, stromal cells are important for the maturation observed when cells are cultured in flat-bottomed wells. We hypothesized that stromal cells may attract B-cell progenitors and promote contacts between responsive cells, a phenomenon that is mimicked by the cultures in round-bottomed wells. In this study, we explore how stromal cells accomplish these functions. We show that stromal cells attract B-cell progenitors in a pertussis toxin-sensitive manner. The stromal cell line S17 produces the chemokine CXCL12, which is able to induce the chemotaxis of B-lineage progenitors. Chemotaxis can be blocked by a small peptide inhibitor (T134) of CXCR4, the CXCL12 receptor. Further, disrupting chemotaxis can reduce the supportive role played by S17 when B-lineage progenitors are cultured in flat-bottomed wells.

Animals↗
PubMed1994

Regulation of alveolar epithelial cell ICAM-1 expression by cell shape and cell-cell interactions.

In normal lung, intercellular adhesion molecule 1 (ICAM-1) is expressed at high levels on thin type I alveolar epithelial cells, but is minimally expressed on cuboidal type II cells. ICAM-1 is induced in primary culture on tissue culture-treated plastic as type II cells undergo transition toward a type I cell-like phenotype. We hypothesized that alveolar epithelial cell expression of ICAM-1 might be regulated in part by signals that influence the state of differentiation of these cells. We found that rat type II cells that were cultured as aggregates of cuboidal cells on a hydrated basement membrane gel (Matrigel) or on floating type I collagen gels, expressed markedly less ICAM-1 protein and mRNA compared with cells that had spread on plastic. In contrast, type II cells that had spread as monolayers on dishes coated with basement membrane proteins in planar configuration demonstrated ICAM-1 expression comparable to that of cells on plastic alone. Thus regulation of alveolar epithelial cell expression of this immunologically important adhesion molecule involves complex spatial interactions of the cells with the basement membrane and other epithelial cells.

Animals↗
PubMed2001

p120 catenin affects cell motility via modulation of activity of Rho-family GTPases: a link between cell-cell contact formation and regulation of cell locomotion.

The molecular basis for contact inhibition of cell locomotion is still largely unknown. Cadherins, the major receptors mediating cell-cell adhesion, associate in the cytoplasm with armadillo family proteins, including beta- and gamma-catenin and p120 catenin (p120ctn). E-cadherin-mediated contact formation was shown to inhibit cellular motility. We examine whether p120ctn may have a role in this regulation. We show here that overexpression of p120ctn in fibroblasts and epithelial cells induces pronounced changes in cell shape, motility and adhesion to the extracellular matrix. p120ctn-transfected cells display increased filopodial/lamellipodial activity, decreased contractility and focal adhesion formation, and augmented migratory ability. These effects of p120ctn are mediated by small GTPases of the Rho family. Direct assessment of the activity of these GTPases in cells expressing a 5-fold higher level of p120ctn as compared to non-transfected control cells revealed significant augmentation of Cdc42 and Rac activity. Moreover, co-transfection of p120ctn with dominant-negative Cdc42 and Rac, or constitutively active Rho suppressed morphological effects of p120ctn. Confocal immunofluorescence visualization of the distribution of endogenous p120ctn in dense cultures showed that formation of cadherin-mediated cell-cell contacts is accompanied by sequestering of p120ctn to the junction regions. In sparse cultures p120ctn is distributed over the cytoplasm. Co-transfection with an excess of E-cadherin leads to sequestration of exogenous p120ctn to cell-cell junctions or to small cadherin-containing vesicles, and abolishes p120ctn effects on cell morphology. Thus, p120ctn may couple the formation and disruption of cadherin-mediated contacts with regulation of cell motility by triggering pathway(s) affecting Rho family GTPases.

Animals↗
PubMed1993

Characterization of cell-adhesive proteins secreted by cell lines growing in protein- and lipid-free synthetic medium: mouse L.P3 cells secrete a procollagen molecule with potent cell-attachment activity.

We have previously shown that mouse L.P3 cells secrete fibronectin and a novel protein, gelatin-non-binding and heparin-binding cell-adhesive protein (GNCP). Here, we screened and characterized cell-adhesive proteins in the conditioned media (CM's) of a series of cell lines growing in a protein- and lipid-free synthetic medium (P3 cell lines). Although cell-attachment activity of the CM's ranged from undetectable to highly significant, fractionation with affinity columns revealed the presence of significant cell-attachment activity in all CM's. Using cell-attachment assay and immunoassay on blotted filters, various cell-adhesive proteins were detected in the CM's, and most of them were identified as fibronectin, laminin, vitronectin, and collagen. GNCP-like proteins were detected in the CM's of HeLa.P3, JTC-16.P3, L.P3, and JTC-12.P3. There was no relationship between the origin of the cell lines and the cell-adhesive proteins secreted. GNCP purified from L.P3-CM was separated into 120-, 140-, 150-, and 160-kDa proteins on SDS-PAGE, which were judged to be a type of mouse type I procollagen from the following results: (1) they were digested by collagenase, (2) pepsin treatment converted the 150- and 160-kDa proteins into 120- and 140-kDa proteins, (3) they were recognized by anti-type I collagen antiserum, and (4) amino-terminal sequence of the pepsin-digested 140-kDa protein had significant homology with type I collagen. GNCP showed half-maximum activity of cell attachment at 0.03 micrograms/ml, indicating that GNCP was a cell-adhesive protein with an extremely high specific activity compared to other known cell-adhesive proteins.

Amino Acid Sequence↗
PubMed1999

IFN-gamma- and cell-to-cell contact-dependent cytotoxicity of allograft-induced macrophages against syngeneic tumor cells and cell lines: an application of allografting to cancer treatment.

In allogeneic tumor or skin transplantation, the rejection process that destroys the allogeneic cells leaves syngeneic cells intact by discrimination between self and nonself. Here, we examined whether the cells infiltrating into the allografts could be cytotoxic against syngeneic immortal cells in vitro and in vivo. The leukocytes (i.e., macrophages (Mphi; 55-65% of bulk infiltrates), granulocytes (20-25%), and lymphocytes (15-20%)) infiltrating into allografts, but not into autografts, in C57BL/6 mice were cytotoxic against syngeneic tumor cells and cell lines, whereas the cytotoxic activity was hardly induced in allografted, IFN-gamma-/- C57BL/6 mice. Among the leukocytes, Mphi were the major population of cytotoxic cells; and the cytotoxic activity appeared to be cell-to-cell contact dependent. When syngeneic tumor cells were s.c. injected into normal C57BL/6 mice simultaneously with the Mphi-rich population or allogeneic, but not syngeneic, fibroblastic cells, tumor growth was suppressed in a cell number-dependent manner, and tumor cells were rejected either with a Mphi:tumor ratio of about 30 or with an allograft:tumor ratio of approximately 200. In the case of IFN-gamma-/- C57BL/6 mice, however, the s.c. injection of the allograft simultaneously with tumor cells had no effect on the tumor growth. These results suggest that allograft or allograft-induced Mphi may be applicable for use in cancer treatment and that IFN-gamma induction by the allograft may be crucial for the treatment.

3T3 Cells↗
PubMed1992

Reversible G1 arrest induced by dimethyl sulfoxide in human lymphoid cell lines: kinetics of the arrest and expression of the cell cycle marker proliferating cell nuclear antigen in Raji cells.

In order to elucidate further the mechanism of reversible cell cycle arrest induced by treatment of Raji cells with 1.5% dimethyl sulfoxide (DMSO), we have performed a detailed analysis of the kinetics of arrest and of reentry into the cell cycle after removal of DMSO and have correlated cell cycle progression with expression of proliferating cell nuclear antigen (PCNA). No significant effect of DMSO on cell cycle patterns, assessed by flow cytometric analysis of bromodeoxyuridine-prelabeled cells, was seen for the first 19 h of treatment. A clear reduction of entry into S phase was detected by about 25 h of treatment; essentially all cells were arrested with a G1 content of DNA after 96 h of treatment. When DMSO-arrested cells were released from the block, entry into S phase began at 12 h after release and continued in a fairly asynchronous manner for a further 12-14 h. In arrested cells, the content of PCNA was reduced to about 25% of the amount present in logarithmically growing G1 phase cells. Six h after release from DMSO, PCNA RNA transcripts were first detected by Northern blotting. The increase of PCNA protein, detected by Western blotting, was seen by 9 h after release. The kinetics of entry into the cell cycle and restoration of PCNA protein are similar to that seen in serum stimulation of quiescent cells. These results suggest that DMSO reversibly arrests proliferation of Raji cells at G0 or at an early point in G1 phase and that progression through late G1 phase and entry into S phase are correlated with synthesis of the PCNA gene product.

Antigens, Neoplasm↗
PubMed1990

Specific recognition of human leukemic cells by allogeneic T cells: II. Evidence for HLA-D restricted determinants on leukemic cells that are crossreactive with determinants present on unrelated nonleukemic cells.

Transplantation of immunocompetent cells present within allogeneic bone marrow has been associated with the elimination of residual host leukemia, both in animal tumor models and in patients receiving marrow transplants for leukemia. This observation has been called the "graft-versus-leukemia effect." We have attempted to study this phenomenon in vitro by characterizing the cytolytic response of T cells from normal donors after in vitro activation with allogeneic leukemic cells. As expected, most T cells that react against an allogeneic patient's leukemic cells recognize their foreign HLA antigens and lyse the patient's nonleukemic remission lymphoid cells. In addition, we have shown that a small fraction of the T cells recognize and lyse foreign leukemic targets without lysis of nonmalignant remission targets from the same leukemic patient. These T cells have been isolated and characterized as CD3+, CD4+ cells expressing the alpha/beta T cell receptor (TCR). Their lysis appears to reflect specific antigen recognition mediated via the CD3-TCR complex and interactions involving the CD4 receptor. Some of these "leukemic specific" T cell lines, which are restricted by HLA class II molecules, can also lyse occasional nonleukemic cells from certain unrelated donors. This recognition appears to involve crossreactive determinants shared by the leukemic cells and the unrelated allogeneic nonleukemic cells. These specific interactions may represent an in vitro model of the graft-versus-leukemia effect.

Antigens↗
PubMed1988

Glandular cell properties of cell line (HKUS) derived from small cell non-keratinizing squamous cell carcinoma of the uterine cervix.

HKUS cell line was established by culturing a uterine cervical small cell non-keratinizing squamous cell carcinoma from a 70-year-old woman. The cells were spindle-like and roundish in shape and in an epithelial cell arrangement. No contact inhibition was observed, and the cells proliferated in multi-layer fashion. Proliferation was quick and more than 250 passages were observed within 4 years after establishment. The chromosome number mode was found in the diploid range, and the chromosomes of stem cells showed a structure abnormality of 45, X, -X. Most HKUS cells had characteristics of glandular cells, and adenocarcinoma was formed when the cells were transplanted into the subepidermis of nude mouse. Some HKUS cells had characteristics of squamous epithelial cells. The HKUS line is regarded as a primitive carcinoma cell line that can differentiate into squamous cell carcinoma and adenocarcinoma.

Adenocarcinoma↗
PubMed1988

Establishment of a human ovarian clear cell carcinoma cell line (RMG-I) and its single cell cloning--with special reference to the stem cell of the tumor.

A cell line, designated RMG-I, has been established from ascites of a patient with ovarian clear cell carcinoma. RMG-I cells have grown well for more than 6 years with mirror ball formation. Chromosome analysis revealed aneuploidy with a modal number of 47 and 3 marker chromosomes. The histological characteristics of the transplanted tumor were similar to those observed in the original tumor which was composed of dark cells, clear cells, and hobnail cells. Thus, the RMG-I cell line was identified to be an ovarian clear cell carcinoma. Immunohistochemically, basic fetoprotein (BFP) and ferritin were demonstrated in the original tumor, the cultured cells, and the transplanted tumor. Furthermore, in order to clarify whether these 3 kinds of cells originate from one stem cell or not, monoclonal cell population were transplanted into nude mice, and its histological investigation revealed that 3 types of cells existed in the transplanted tumor, proving that they originate from one stem cell.

Adenocarcinoma↗