lewis-x-antigen and Cell-Transformation--Neoplastic

Various cell surface markers, such as SSEA-1, SSEA-3, Forssman, I, i, brushin, FT-1, PNA receptors, FBP receptors, and DBA receptors, are expressed in certain subpopulations of early embryonic cells. They are useful in monitoring the process of in vitro differentiation of embryonal carcinoma (EC) cells. For example, SSEA-1 is a marker of EC cells, whereas DBA receptors are markers of endoderm cells and quasi-nullipotent EC cells. An important carrier of the developmentally regulated cell surface markers is embryoglycan, which is a class of glycoprotein-bound large carbohydrates and has the lactosaminoglycan-type structure.

Topics: Antigens, Neoplasm; Antigens, Surface; Cell Transformation, Neoplastic; Glycolipids; Glycoproteins; Lewis X Antigen; Polysaccharides; Receptors, Mitogen; Teratoma

Topics: Biopsy, Fine-Needle; Cell Transformation, Neoplastic; Diagnosis, Differential; Hodgkin Disease; Humans; Ki-1 Antigen; Leukemia, Lymphocytic, Chronic, B-Cell; Lewis X Antigen; Lymphadenopathy; Male; Middle Aged

In patients with chronic Helicobacter pylori (H pylori) infection, parietal and chief cell atrophy in the gastric corpus, a process known as spasmolytic polypeptide-expressing metaplasia (SPEM), increases the risk for progression to cancer. The relation between H pylori and these metaplastic changes is unclear. We investigated whether H pylori localizes to regions of SPEM.. We developed an in situ adherence assay in which we incubated H pylori with free-floating tissue sections from the gastric corpora of mice; we assessed H pylori distribution along the gastric unit by immunofluorescence. We analyzed the interactions of H pylori with tissue collected from mice with acute SPEM, induced by high-dose tamoxifen. We also evaluated how adhesin-deficient H pylori strains, chemical competition assays, and epithelial glycosylation affected H pylori adhesion to SPEM glands. Mice colonized with the mouse-adapted PMSS1 strain were analyzed for H pylori colonization in vivo during tamoxifen-induced SPEM or after decrease of stomach acid with omeprazole.. Compared with uninjured glands, H pylori penetrated deep within SPEM glands, in situ, through interaction of its adhesin, SabA, with sialyl-Lewis X, which expanded in SPEM. H pylori markedly increased gastric corpus colonization when SPEM was induced, but this proximal spread reversed in mice allowed to recover from SPEM. Decreasing corpus acidity also promoted proximal spread. However, H pylori penetrated deep within corpus glands in vivo only when sialyl-Lewis X expanded during SPEM.. Helicobacter pylori differentially binds SPEM glands in situ and in mice, in large part by interacting with sialyl-Lewis X. Our findings indicate that H pylori expands its niche into the gastric corpus by promoting and exploiting epithelial metaplastic changes that can lead to tumorigenesis.

Topics: Adhesins, Bacterial; Animals; Bacterial Adhesion; Cell Transformation, Neoplastic; Disease Models, Animal; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Host-Pathogen Interactions; Humans; Intercellular Signaling Peptides and Proteins; Lewis X Antigen; Male; Metaplasia; Mice; Peptides; Sialyl Lewis X Antigen

: Acquired expression of CD30 is frequently noted in histological transformation of mycosis fungoides (MF), but simultaneous gain of CD15 accompanied with loss of pan-T-cell antigens are extremely rare. We report an unusual case of transformed MF with such an immunophenotypic alteration resembling classical Hodgkin lymphoma. The patient was an 81-year-old male with MF, who was initially treated with topical steroids and phototherapy. Despite the initial response, the patient developed a tumor-like skin lesion that was confirmed to be CD30-positive large T-cell lymphoma and was subsequently found to have a regional lymph node involvement by pleomorphic large cell lymphoma. Besides CD30, pleomorphic large cells were positive for CD15 but negative for all B cell- and T cell-specific antigens. Epstein-Barr virus was negative. Polymerase chain reaction-based assays demonstrated a clonal rearrangement of T-cell receptor gamma gene but detected no B-cell clone. The mechanism and clinical significance of this phenotypic conversion remains to be elucidated.

Topics: Aged, 80 and over; Biomarkers, Tumor; Cell Transformation, Neoplastic; Fucosyltransferases; Hodgkin Disease; Humans; Immunophenotyping; Ki-1 Antigen; Lewis X Antigen; Lymphoma, Primary Cutaneous Anaplastic Large Cell; Male; Mycosis Fungoides; Skin Diseases

Cancer stem cells (CSCs) are the most aggressive cell type in many malignancies. Cell surface proteins are generally used to isolate and characterize CSCs. Therefore, the identification of CSC-specific cell surface markers is very important for the diagnosis and treatment of malignancies. We found that Nestin (a type VI intermediate filament protein), like the glioma stem cell (GSC) markers CD133 and CD15, exhibited different levels of expression in primary human glioblastoma specimens. Similar to our previous finding that cytoplasmic Nestin is expressed as a cell surface form in mouse GSCs, the cell surface form of Nestin was also expressed at different levels in human GSCs. We isolated cell surface Nestin-positive cell populations from human GSCs by fluorescence-activated cell sorting FACS analysis, and observed that these populations exhibited robust CSC properties, such as increased tumorsphere-forming ability and tumorsphere size. Mechanistically, we found that DAPT, a γ-secretase (a multi-subunit protease complex) inhibitor, reduced the proportion of cell surface Nestin-positive cells in human GSCs in a time- and dose-dependent manner, without significant changes in total Nestin expression, implying that a post-translational modification was involved in the generation of cell surface Nestin. Taken together, our data provides the first evidence that cell surface Nestin may serve as a promising GSC marker for the isolation and characterization of heterogeneous GSCs in glioblastomas.

Topics: AC133 Antigen; Amyloid Precursor Protein Secretases; Antigens, CD; Biomarkers, Tumor; Cell Shape; Cell Transformation, Neoplastic; Flow Cytometry; Fluorescent Antibody Technique; Fucosyltransferases; Gene Expression Regulation, Neoplastic; Glioblastoma; Glycoproteins; Humans; Intermediate Filament Proteins; Lewis X Antigen; Neoplastic Stem Cells; Nerve Tissue Proteins; Nestin; Peptides; Protein Processing, Post-Translational; Reproducibility of Results; Single-Cell Analysis; Tumor Cells, Cultured

The MLL-AF9 fusion gene is associated with aggressive leukemias of both the myeloid and lymphoid lineage in infants, whereas in adults, this translocation is mainly associated with acute myeloid leukemia. These observations suggest that differences exist between fetal and adult tissues in terms of the 'cell of origin' from which the leukemia develops. Here we show that depending on extrinsic cues, human neonatal CD34(+) cells are readily immortalized along either the myeloid or lymphoid lineage upon MLL-AF9 expression and give rise to mainly lymphoid leukemia in immunocompromised mice. In contrast, immortalization of adult bone marrow CD34(+) cells is more difficult to achieve and is myeloid-biased, even when MLL-AF9 is expressed in purified hematopoietic stem cells (HSCs). Transcriptome analysis identified enrichment of HSC but not progenitor gene signatures in MLL-AF9-expressing cells. Although not observed in adult cells, neonatal cells expressing MLL-AF9 were enriched for gene signatures associated with poor prognosis, resistance to chemotherapeutic agents and MYC signaling. These results indicate that neonatal cells are inherently more prone to MLL-AF9-mediated immortalization than adult cells and suggest that intrinsic properties of the cell of origin, in addition to extrinsic cues, dictate lineage of the immortalized cell.

Topics: Animals; Antigens, CD19; Cell Lineage; Cell Transformation, Neoplastic; Female; Hematopoietic Stem Cells; Humans; Infant, Newborn; Leukemia, Myeloid, Acute; Lewis X Antigen; Lipopolysaccharide Receptors; Mice; Mice, SCID; Myeloid-Lymphoid Leukemia Protein; Oncogene Proteins, Fusion; Precursor Cell Lymphoblastic Leukemia-Lymphoma

The cytological origin of central nervous system hemangioblastoma (HB) remains unclear and controversial, largely owing to a lack of in-depth characterization of tumorigenic cells and their progeny tracking. We have now detected a cell subpopulation by stage-specific embryonic antigen-1 expression, which were defined as tumor-initiating cells (TICs) in both sporadic and familial HBs. These TICs subpopulations had universal neural stem cell characteristics. Nevertheless, the freshly sorted TICs endowed with potential of multi-progeny derivatives, including HB components and non-HB ingredients, depended on environmental induction in vitro. Importantly, the freshly harvested TICs formed malignant tumors by injection into conventional mice model, while did redevelop the characteristic HB-like structures within a special mice model with HB-microenvironment, indicating HB niche dependency for the TICs derivative specification. Taken together, the data of the present study suggested that HBs might derive from neoplastic transformation of neural stem cells/progenitors in the specific niche.

Topics: Adolescent; Adult; Aged; Animals; Blotting, Western; Cell Differentiation; Cell Lineage; Cell Separation; Cell Transformation, Neoplastic; Cerebellar Neoplasms; Female; Flow Cytometry; Hemangioblastoma; Humans; Immunohistochemistry; Lewis X Antigen; Male; Mice; Middle Aged; Neoplastic Stem Cells; Neural Stem Cells; Stem Cell Niche; Young Adult

The cytological origin of hemangioblastomas (HBs) is controversial possibly owing to limitation in the framework of normal vascular development. Our previous study reported that SSEA1 (stage-specific embryonic antigen-1) cells had the potential of HB-like structure formation in vitro cellular models. Here, we characterized primary proliferating tumor-initiating cells (TICs) and their neoplasmtic transformation. Neural stem cell marker SSEA1 and its lineage-related genes were demonstrated; no embryonic and mesenchymal stem cell markers were detected whereas their lineage-related genes in part were activated. Immunohistochemistry showed that the proliferating marker was preferentially expressed in SSEA1 cells. There was significant difference in the percentage of SSEA1 cells (SSEA1+/Ki67+ cells) between inherited and sporadic HBs although the tumor proliferative index (Ki67+ cells/ all cells) did not reach statistical significance between the two groups. Further, corresponding to the morphological changes of nucleolus in number and size, these highly proliferating SSEA1 cells demonstrated coexpression of either D2-40 or the mesodermal marker Scl (stem cell leukemia), brachyury, and Flk-1 (vascular endothelial growth factor-2), respectively, indicative of the neoplasmtic transformation into the stromal or vascular cells. The present data suggest that HBs might derive from neoplastic transformation of neural stem cells/progenitors. Such findings also provide new insights into the biology of HBs and the definition of TICs in situ, as well as the mechanisms of tumor neovascularization.

Topics: Adolescent; Adult; Aged; Cell Differentiation; Cell Growth Processes; Cell Transformation, Neoplastic; Cerebellar Neoplasms; Child; Female; Hemangioblastoma; Humans; Immunohistochemistry; Lewis X Antigen; Male; Mesenchymal Stem Cells; Middle Aged; Neural Stem Cells; Young Adult

Cancer stem cells (CSCs) have been implicated in the maintenance and progression of several types of cancer. The origin and cellular properties of human CSCs are poorly characterized. Here we show that CSC-like cells can be generated in vitro by oncogenic reprogramming of human somatic cells during neoplastic transformation. We find that in vitro transformation confers stem-cell properties to primary differentiated fibroblasts, including the ability to self-renew and to differentiate along multiple lineages. Tumours induced by transformed fibroblasts are hierarchically organized, and the cells that act as CSCs to initiate and maintain tumour growth are marked by the stage-specific embryonic antigen SSEA-1. Heterogeneous lineages of cancer cells in the bulk of the tumour arise through differentiation of SSEA-1(+) fibroblasts, and differentiation is associated with loss of tumorigenic potential. These findings establish an experimental system to characterize cellular and molecular properties of human CSCs and demonstrate that somatic cells have the potential to de-differentiate and acquire properties of CSCs.

Topics: Animals; Blotting, Western; Cell Differentiation; Cell Line; Cell Lineage; Cell Proliferation; Cell Transformation, Neoplastic; Fibroblasts; Gene Expression Profiling; Green Fluorescent Proteins; Humans; Lewis X Antigen; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Fluorescence; Neoplasms, Experimental; Neoplastic Stem Cells; Oligonucleotide Array Sequence Analysis; Transplantation, Heterologous

Warthin tumor-like variant of papillary thyroid carcinoma is uncommon and approx 80 cases have been reported in the literature. This tumor is often associated with a favorable prognosis. In this report, a Warthin tumor-like variant of the papillary thyroid carcinoma, 5-cm in maximum dimension, underwent anaplastic changes in a 74-yr-old woman. The tumor was positive for CD15 and EMA, and a high proliferative index was noted in the anaplastic area. The patient developed distant metastases after operation and died of the disease 18 mo after the operation. The present case is the first reported case of Warthin tumor-like variant of papillary thyroid carcinoma with anaplastic changes.

Topics: Adenolymphoma; Aged; Biomarkers, Tumor; Carcinoma, Papillary; Cell Proliferation; Cell Transformation, Neoplastic; Fatal Outcome; Female; Humans; Lewis X Antigen; Mucin-1; Radiotherapy, Adjuvant; Thyroid Neoplasms

Large cell lymphomas and Hodgkin disease may develop during the course of chronic lymphocytic leukemia (CLL). In some cases the transformed cells are Epstein-Barr virus (EBV)-positive and not clonally related to the CLL cells. In other cases the transformed cells have the same clonal rearrangements as the CLL cells. Here we describe a composite lymphoma in a patient with CLL that exhibits a combination of CLL/small lymphocytic lymphoma, large cell lymphoma with anaplastic morphology, and Hodgkin lymphoma (HL). Although the large cell lymphoma cells are CD45R0 and TIA-1-positive, suggesting a T- or 0-cell anaplastic large cell lymphoma (ALCL), the genetic analysis demonstrates immunoglobulin heavy chain (IgH) gene rearrangements for both alleles, carrying the same somatic mutations as observed in the CLL component. The Reed-Sternberg (R-S) cells in the Hodgkin component also strongly express TIA-1 but differ from the anaplastic large cells by the expression of CD15 and TARC and the presence of a prominent lymphocytic infiltrate. The ALCL and HL components both are EBV negative. Analysis of the IgH gene rearrangements in micromanipulated R-S cells revealed identical Ig gene rearrangements carrying the same somatic mutations as the CLL and the large cell components. The findings indicate transformation of the CLL cells into a large cell lymphoma with anaplastic morphology and a Hodgkin component.

Topics: Aged; Base Sequence; Cell Transformation, Neoplastic; Chemokine CCL17; Chemokines, CC; Clone Cells; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Herpesvirus 4, Human; Hodgkin Disease; Humans; Immunoglobulin Heavy Chains; Immunophenotyping; Leukemia, Lymphocytic, Chronic, B-Cell; Lewis X Antigen; Lymphoma, Large B-Cell, Diffuse; Male; Membrane Proteins; Molecular Sequence Data; Mutation; Poly(A)-Binding Proteins; Proteins; Reed-Sternberg Cells; RNA-Binding Proteins; T-Cell Intracellular Antigen-1

Renal cell carcinoma (RCC) arising in acquired cystic kidney disease (ACKD) is considered to be a tumor of low malignant potential, compared with classic RCC. The aim of the present study was to identify any significant differences in the antigenic profiles or tumor cell proliferative activity of ACKD-associated RCC and classic RCC that might be responsible for differences in their biologic behavior. We studied the immunohistochemical profiles and proliferative activity of 12 classic RCCs and 5 ACKD-associated RCCs with markers of proximal tubules (Leu M1, alpha-1 antitrypsin, CAM 5.2), markers of distal tubules (Arachis hypogaea lectin, AE1/AE3, epithelial membrane antigen [EMAJ, CAM 5.2), vimentin, and proliferating cell nuclear antigen (PCNA). We performed proliferation analysis with the CAS 200 image analysis system. For each case, 8 to 20 fields of tumor tissue in the areas of maximal PCNA staining were quantitated, and the percentage of PCNA-positive nuclear area for each individual tumor was calculated. All of the five ACKD-associated RCCs expressed AE1/AE3, EMA, and CAM 5.2 in more than 50% of the tumor cells. Arachis hypogaea lectin was significantly expressed in three of the five ACKD-associated RCCs. Leu M1 and alpha-1 antitrypsin reacted with fewer than 10% of the tumor cells in all of the five ACKD-associated RCCs. In contrast, the 12 classic RCCs showed expression of CAM 5.2 in 11 cases, alpha-1 antitrypsin in 10 cases, Leu M1 in 9, EMA in 8, and AE1/AE3 in 3 cases in more than 50% of the tumor cells and a totally negative reaction with Arachis hypogaea lectin in 8 cases, EMA in 4, AE1/AE3 in 4, and vimentin in 5 cases. Although coexpression of proximal and distal tubule markers was seen in some cases of RCC in either category, there was uniform and strong staining for distal tubule markers in ACKD-associated RCC and for proximal tubule markers in classic RCC. The mean percentage of PCNA-positive nuclear area for the ACKD-associated RCCs (2.41%) was significantly (P < .05) less than that of the classic RCCs (21.42%). The differences in expression of proximal and distal tubule markers and proliferative activity might be responsible for the differences in the biologic behavior of ACKD-associated RCC and classic RCC.

Topics: Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Analysis of Variance; Biomarkers, Tumor; Carcinoma, Renal Cell; Cell Nucleus; Cell Transformation, Neoplastic; Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Kidney Diseases, Cystic; Kidney Neoplasms; Kidney Tubules; Lewis X Antigen; Male; Middle Aged; Mucin-1; Peanut Agglutinin; Proliferating Cell Nuclear Antigen; Vimentin

Fifty esophageal adenocarcinomas were investigated for their expression of Le(a), Le(x), and Le(a)-Le(x). Among the 50 adenocarcinomas, 17 cases developed in Barrett's epithelium. Those 17 differed from the other 33 cases by expressing much less Le(x). Fifty-nine percent of Barrett's adenocarcinomas were Le(x) negative compared with 24% of the non-Barrett's carcinomas. All Barrett's adenocarcinomas showed less than 50% Le(x) whereas 50% of non-Barrett's carcinomas showed between 50 and 100% expression. The statistical correlation coefficient for this association was P < 0.001. Normal gastric cardia epithelium showed the same Le(x) expression in both groups. In the Barrett group, Le(x) expression decreased from normal through intestinal metaplasia and dysplasia to adenocarcinoma. This progression was not seen in the non-Barrett group. Loss of Le(x) expression may prove useful in following patients with Barrett's epithelium in evaluating progression toward a malignant process. No difference in expression of Le(a) and Le(a)-Le(x) was found between Barrett's and non-Barrett's carcinomas.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Cell Transformation, Neoplastic; Epithelium; Esophageal Neoplasms; Esophagus; Female; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Lewis X Antigen; Male; Middle Aged; Precancerous Conditions; Prognosis

We describe the histologic and immunohistochemical findings in specimens from bone marrow (BM) biopsies performed for staging purposes in 13 patients with a previous tissue-based diagnosis of T-cell-rich B-cell lymphoma (TCRBCL). Bone marrow involvement was found in 8 (62%) of 13 cases and was often paratrabecular. The histologic appearance was not pathognomonic of TCRBCL, with the differential diagnosis including Hodgkin's disease and peripheral T-cell lymphoma. The infiltrates typically had a pale low-power appearance (due to histiocytic infiltration, relative hypocellularity, or both) that, in conjunction with the presence of a polymorphous infiltrate of scattered large atypical cells amid a mixed infiltrate of small lymphocytes and histiocytes, was suggestive of Hodgkin's disease. Immunohistochemistry revealed CD20 reactivity of the large atypical cells with the absence of CD15 and CD30 reactivity, supporting the diagnosis of TCRBCL. A prominent small T-cell infiltrate accompanying the large atypical cells was observed in all positive BM biopsy specimens. The increased incidence of BM involvement in TCRBCL is significantly higher than that found in de novo B-cell diffuse large cell lymphoma, suggesting a possible biologic difference between the two entities. Our cases share some similar clinicopathologic features with histiocyte-rich B-cell lymphoma and with diffuse lymphocyte-predominant Hodgkin's disease, paragranuloma type. We discuss the possible relationship to these two entities.

Topics: Adult; Aged; Antigens, CD20; Biopsy; Bone Marrow; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; Genotype; Hodgkin Disease; Humans; Immunohistochemistry; Immunophenotyping; Ki-1 Antigen; Lewis X Antigen; Lymph Nodes; Lymphoma, B-Cell; Lymphoma, T-Cell; Male; Middle Aged; Survival Rate; T-Lymphocytes

The pathogenesis of Reed-Sternberg cells and variants (RS-H cells) found in rare cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is unknown. We studied 13 such cases by immunohistochemistry and in situ hybridization for identification of Epstein-Barr virus (EBV) RNA. The RS-H cells in five cases expressed the B-lineage marker CD20 and were negative for CD15. In two cases, the RS-H cells showed expression of both CD20 and CD15, whereas in another six cases, the cells were positive for CD15 but negative for CD20. Three of the cases expressing CD15 showed subsequent evidence of disseminated Hodgkin's disease. Regardless of the phenotype or clinical behavior, the RS-H cells in 12 of 13 cases were found to contain EBV RNA by in situ hybridization, but the surrounding neoplastic lymphocytes were invariably negative for EBV RNA. It is suggested that EBV has an important role in the pathogenesis of the RS-H cells in these rare cases.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, CD20; Antigens, Differentiation, B-Lymphocyte; Cell Transformation, Neoplastic; DNA, Viral; Female; Herpesvirus 4, Human; Hodgkin Disease; Humans; Immunohistochemistry; Leukemia, Lymphocytic, Chronic, B-Cell; Lewis X Antigen; Male; Middle Aged; Nucleic Acid Hybridization; Phenotype; Reed-Sternberg Cells; RNA, Viral

Differentiation of the F9 cell line was induced by treating the cells with retinoic acid (10(-6) M) and dibutyryl cycloadenosinemonophosphate (10(-4) M). The population doubling time and the portion of cells in G1-phase increase and saturation density falls as the result of this treatment. Differentiated F9 cells demonstrate a decreased capacity of forming colonies in the soft agar, lose their capacity of proliferating at the clonal density, and acquire the limited life-span in culture after reseeding at a high density. Some cells in the differentiated population retain their capacity of forming colonies in the soft agar and (or) of binding antibodies against the stem cell marker SSEA-1. Cells with the stem cell morphology were found in the course of passaging of differentiated cells after reseeding at a high density. These cells were able to differentiate after the standard procedure of the induction of differentiation with retinoic acid and dibutyryl cAMP. Causes of the rising and supporting of heterogeneity of the differentiated F9 cells are discussed.

Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Bucladesine; Cell Division; Cell Line, Transformed; Cell Transformation, Neoplastic; Glycolipids; Lewis X Antigen; Mice; Phenotype; Teratoma; Tretinoin; Tumor Cells, Cultured

The epithelial expression of carbohydrate antigen, stage-specific embryonic antigen 1 (SSEA-1) was examined immunohistochemically in noncancerous specimens from patients with familial polyposis coli, and compared with the colorectal epithelia from patients with sporadic colorectal cancer. In mucosa remote from carcinoma of sporadic cases, SSEA-1 was expressed only faintly in the lower crypts. In mucosa adjacent to carcinoma of sporadic cases, SSEA-1 was expressed not only in the lower crypts but also in the upper crypts. These results corresponded to those observed in the authors' previous study. In the flat mucosa of familial polyposis coli cases, SSEA-1 was detected not only in the lower crypts, but also in both upper crypts and the surface epithelium in contrast with the flat mucosa of sporadic cases. The staining pattern in the upper crypts of the flat mucosa of familial polyposis coli cases was very similar to that of the mucosa adjacent to carcinoma of sporadic cases, but was stronger and more diffuse in the surface epithelium. In microscopic adenomas, SSEA-1 was expressed diffusely. These results demonstrate that the flat mucosa of patients with familial polyposis coli shows preneoplastic changes similar to those in the mucosa adjacent to carcinoma of sporadic cases, and that SSEA-1 is related to adenoma formation in the early stage of carcinogenesis in the colorectum. In addition, the results suggest that immunohistochemical studies of flat mucosa may be useful for the early detection of high-risk individuals in a familial polyposis coli family.

Topics: Cell Transformation, Neoplastic; Colonic Neoplasms; Colonic Polyps; Glycolipids; Humans; Intestinal Mucosa; Lewis X Antigen

Colorectal carcinomas are composed of heterogeneous cell subpopulations which may be instrumental in conferring metastatic potential and therapeutic refractoriness to these tumours. To assess cellular heterogeneity, the expression has been examined of two oncodevelopmental antigens, carcinoembryonic antigen (CEA) and stage-specific embryonic antigen 1 (SSEA-1), by double immunofluorescence microscopy on 11 human colorectal carcinomas. Although both antigens were expressed in each tumour, their regional and cellular locations differed considerably. SSEA-1 expression was rarely expressed in poorly differentiated cancers but was enhanced with increasing degrees of differentiation. CEA expression was independent of histological differentiation. SSEA-1 was expressed with similar frequency in cell membranes, cytoplasm, and glandular contents regardless of degree of differentiation. Cytoplasmic staining with CEA however, was limited to more poorly differentiated tumours. In normal mucosa remote from the tumours and transitional mucosa adjacent to them, SSEA-1 stained only a few lower crypts whereas CEA stained a majority of both upper and lower crypts. Although biochemical studies have indicated that the SSEA-1 epitope may reside on CEA molecules, the fact that colon cancer tissues express these two antigens quite heterogeneously suggests differences in antigenic processing which may be dependent upon the degree of cellular differentiation.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigen-Antibody Complex; Carcinoembryonic Antigen; Cell Transformation, Neoplastic; Colonic Neoplasms; Glycolipids; Humans; Intestinal Mucosa; Lewis X Antigen; Neoplasm Staging; Rectal Neoplasms; Reference Values

Previous work has shown that murine embryonal carcinoma cells are refractory to infection with various viruses, including simian virus 40. Thus, large T and small t antigens, the products of the simian virus 40 early region, are not produced when the virus infects embryonal carcinoma cells, in contrast to other cell types. We show, by qualitative and quantitative analyses, that embryonal carcinoma cell hybrids, containing a simian virus 40 early region integrated into human DNA, are capable of producing viral large T antigen.

Topics: Animals; Antigens, Neoplasm; Antigens, Polyomavirus Transforming; Antigens, Viral, Tumor; Cell Line; Cell Transformation, Neoplastic; Embryonal Carcinoma Stem Cells; Fluorescent Antibody Technique; Genes; Genes, Viral; Glycolipids; Humans; Hybrid Cells; Kinetics; Lewis X Antigen; Mice; Neoplastic Stem Cells; Simian virus 40; Teratoma; Viral Proteins

A murine embryonal carcinoma (EC) cell line heterozygous for t0 recessive lethal mutation has been established from an embryo-derived transplantable teratocarcinoma TC1Ph of the genotype (129-T/t0 X C3H/Di)t0/+. The EC cell line, designated EC1Ph, and two cloned sublines, EC1Ph/a and EC1Ph/b, maintain the diploid karyotype (40, XY) and give rise to teratocarcinomas with differentiated derivatives of EC cells after inoculation into syngeneic recipients. The cloned sublines express low or zero amounts of SSEA-1 and ECMA-7 stage-specific antigens. At some passages, the EC1Ph line and the cloned subline EC1Ph/b express a significant quantity of class I H-2 antigens. This unusual EC phenotype resembles that of human teratocarcinoma cell lines.

Topics: Animals; Antigens, Neoplasm; Antigens, Surface; Cell Line; Cell Separation; Cell Transformation, Neoplastic; Clone Cells; Cytological Techniques; Glycolipids; Lewis X Antigen; Mice; Mice, Inbred Strains; Mutation; Neoplasm Transplantation; Phenotype; Radioimmunoassay; Teratoma