Mesenchymal Stem Cell Administration Attenuates Colon Cancer Progression by Modulating the Immune Component within the Colorectal Tumor Microenvironment.

We here determine the influence of mesenchymal stem cell (MSC) therapy on the progression of solid tumors. The influence of MSCs was investigated in human colorectal cancer cells as well as in an immunocompetent rat model of colorectal carcinogenesis representative of the human pathology. Treatment with bone marrow (BM)-derived MSCs significantly reduced both cancer initiation and cancer progression by increasing the number of tumor-free animals as well as decreasing the number and the size of the tumors by half, thereby extending their lifespan.

IR spectral imaging of secreted mucus: a promising new tool for the histopathological recognition of human colonic adenocarcinomas.

Aims: During colonic carcinogenesis, mucin-type glycoproteins are known to undergo quantitative and qualitative alterations. The aim of this study was to determine the value of infrared (IR) spectral histology for the histopathological recognition of colonic adenocarcinomas based on mucin-associated IR spectral markers.

Methods And Results: Paraffin-embedded tissue sections of normal human colon and adenocarcinomas were analysed directly by IR-microspectroscopy (IR-MSP), without prior chemical dewaxing.

Early lesions induced in rat colon epithelium by N-methyl-N'-nitro-N-nitrosoguanidine.

The development of ACF (aberrant crypt foci), adenoma and cancer following intrarectal administration of the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) has been described. However, microscopic lesions not previously reported were observed as soon as two weeks following carcinogen treatment. These lesions protrude slightly over the epithelial lining of the colon, with a micropolyp-like appearance.

Proteases present in some pancreatic cyst fluids may affect mucin immunoassay by degrading antibodies and antigens.

Objectives: Biomarker detection in pancreatic cyst fluids is of importance to improve the diagnosis of mucinous cystadenoma, a precancerous lesion. However, assay protocols are generally established for serum testing.

Methods: Immunoradiometric assay of gastric M1/MUC5AC mucin was performed on pancreatic cyst fluids with well-characterized monoclonal antibodies.

Resistin-like molecule beta regulates intestinal mucous secretion and curtails TNBS-induced colitis in mice.

Background: Resistin and resistin-like molecule (RELM)beta comprise a novel class of cysteine-rich proteins secreted into the circulation implicated in hepatic insulin resistance and inflammation. RELMbeta is specifically produced by intestinal goblet cells but regulation of its expression and much of its local function are not elucidated. RELMbeta has been suggested to regulate colonic inflammation susceptibility, which is dependent on the mucosal barrier integrity.

PAR-2 activation increases human intestinal mucin secretion through EGFR transactivation.

PAR-2 (protease-activated receptors-2) are G protein-coupled receptors whose action on mucin secretion by intestinal epithelial cells is still unknown. The aim of this study was to examine the effect of PAR-2 activation on mucin secretion in the human colonic goblet cell line HT29-Cl.16E and the intracellular pathways involved.

Abnormal expression of M1/MUC5AC mucin in distal colon of patients with diverticulitis, ulcerative colitis and cancer.

The abnormal expression of gastric M1/MUC5AC mucin in precancerous lesions and colon cancer evidenced by immunohistochemistry led us to check for its presence in the mucus obtained directly from patients undergoing surgery for cancerous (adenocarcinoma) or inflammatory (diverticulitis or ulcerative colitis) diseases. In parallel, the authors quantified aberrant crypt foci (ACF) and their immunolabelling by M1/MUC5AC in mucosae of cancer and diverticulitis patients. Immuno-Radio-Metric Assay of M1/MUC5AC mucin developed by the authors was used to detect M1/MUC5AC mucin in the colonic mucus scraped from surgical specimens.

Progression of tumors arising from large ACF is associated with the MUC5AC expression during rat colon MNNG carcinogenis.

Aberrant crypt foci (ACF) are microscopic lesions which have been postulated to precede the development of adenomas, precursors of colon cancer. The gastric M1/MUC5AC mucin has also been described as an early marker of colon carcinogenesis in the human and in the rat. To study changes in mucin expression associated with the genesis of tumors, Wistar rats were treated by intrarectal instillations of MNNG, twice a week for 2 weeks, and were sacrificed 10 (n = 20), 14 (n = 20), 22 (n = 20), 30 (n = 10) and 66 (n = 16) weeks after the beginning of the treatment.

Mapping of SOMU1 and M1 epitopes on the apomucin encoded by the 5' end of the MUC5AC gene.

We have developed 11 monoclonal antibodies (MAbs) against human gastric mucin, (1-13M1, 2-11M1, 2-12M1, 9-13M1, 58M1, 19M1, 21M1, 45M1, 463M, 589M, 62M1), which specifically stained by immunohistochemisty both the human gastric surface mucosa and colon adenoma. Among them, five (19M1, 21M1, 463M, 589M, 62M1) immunoreacted with the peptide encoded by the 3' region of the MUC5AC gene (Nollet et al: Int J Cancer 2002;99:336-343). In this study, we identified in the 5' region of this gene the nucleotide fragments encoding peptides immunoreacting with three other anti-M1 MAbs (1-13M1, 2-11M1 and 9-13M1), as well as the SOMU1 MAb (Sotozono et al: J Immunol Methods 1996;192:187-196).

Abnormal expression of gastric mucin in human and rat aberrant crypt foci during colon carcinogenesis.

Colorectal cancer is a major cause of death in Europe and the USA, and much effort is therefore devoted to improve its early detection. In this article, we report the abnormal expression of gastric mucin in aberrant crypt foci (ACF) that appear in the colon mucosae removed from colorectal cancer patients and rats treated with methyl-N'-nitro-N-nitroso-guanidine (MNNG). We performed the immunoperoxidase test using monoclonal antibodies raised against gastric M1 mucin encoded by the MUC5AC gene and against rat gastric mucins (MAb 660), respectively.

Activation of mucin exocytosis and upregulation of MUC genes in polarized human intestinal mucin-secreting cells by the thiol-activated exotoxin listeriolysin O.

The secreted thiol-activated cytolysin listeriolysin O (LLO) was responsible for L. monocytogenes-induced high-molecular glycoproteins (HMGs) exocytosis in cultured human mucosecreting HT29-MTX cells. By biochemical analysis we demonstrate that the majority of secreted HMGs in LLO-stimulated cells are of mucin origin.

Mapping of two new epitopes on the apomucin encoded by MUC5AC gene: expression in normal GI tract and colon tumors.

Three hybridomas secreting monoclonal antibodies (MAbs) against human (62M MAb) or rat (463M and 589M MAbs) gastric mucins were isolated. These MAbs immunoreacted against a human recombinant protein encoded by the 3' region of the MUC5AC gene. We have mapped 2 new gastric mucin epitopes and the M1-f epitope previously characterized by the 19/21M1 MAbs on MUC5AC-encoded apomucin.

Gastric M1 mucin, an early oncofetal marker of colon carcinogenesis, is encoded by the MUC5AC gene.

Gastric M1 mucin and the MUC5AC gene show a similar oncofetal expression in the colon. Our aim was to determine whether M1 mucin is the product of the MUC5AC gene. A recombinant baculovirus encoding the C-terminal portion of the MUC5AC gene as a fusion protein was isolated and the immunoreactivity of the recombinant mucin (rM) toward M1 antibodies studied.

Detection of gastric mucins (M1 antigens) in cyst fluid for the diagnosis of cystic lesions of the pancreas.

Mucinous cystic tumors of the pancreas must be distinguished from other cystic lesions because of their potential malignancy. Our purpose was to assess the reliability of gastric M1 mucin analysis in the fluid of cystic lesions of the pancreas in comparison or association with carcinoembryonic antigen. M1 mucin and carcinoembryonic antigen were measured in cyst fluid obtained preoperatively by fine-needle aspiration.

Enterocyte differentiation is compatible with SV40 large T expression and loss of p53 function in human colonic Caco-2 cells. Status of the pRb1 and pRb2 tumor suppressor gene products.

Transfer of the SV40 large-T (LT) oncogene into isolated human and murine intestinal epithelial cells induced alterations of the ultrastructural organization and polarization of the resulting immortalized cell lines. We now demonstrate that the functional expression of the SV40 LT antigen in Caco-2 cells did not alter phenotypic markers of differentiation, including expression of villin, sucrase-isomaltase, brush border and dome formation. As compared to parental cells, the transfected Caco-2 LT9 cells exhibited similar growth curves and no invasive properties in vitro.

Devazepide (L-364718) inhibits growth and increases expression of tumor markers in HT29-S-B6 cells.

Devazepide (L-364718, a non-peptide antagonist of CCK-A receptors), inhibits the proliferation and induces morphologic changes in the mucous-secreting, autonomously proliferating human cancer colon cell line (HT29-S-B6. Addition of devazepide (10 microM) for at least 3 days in the exponential phase of growth enhanced the baseline production of gastric M1 mucins 2-3-fold and that of carcinoembryonic antigens 5-fold. Moreover, devazepide induced an increase in the amount of the MUC-5AC mRNA expressed by HT29-S-B6 cells.

Antiproliferative effects of the arotinoid Ro 40-8757 in human gastrointestinal and pancreatic cancer cell lines: combinations with 5-fluorouracil and interferon-alpha.

The arotinoid Ro 40-8757 was previously shown to inhibit the growth of a variety of human cancer cell lines derived from breast, lung and uterus. In view of the high incidence of human digestive cancers, and the slow progress in the development of new therapy, we examined in this paper several combinations between the new arotinoid Ro 40-8757, 5-fluorouracil (5FU) and interferon alpha-2a on the growth of nine human cancer cell lines derived from the gastrointestinal and pancreatic system. Half-maximal inhibition of cell proliferation by Ro 40-8757 was observed at concentrations ranging between 0.

Effects of VIP on the regulation of mucin secretion in cultured human pancreatic cancer cells (Capan-1).

The effects of Vasoactive intestinal peptide (VIP) on mucin secretion in the pancreatic cancer Capan-1 cell line were studied by Enzyme-linked-immunosorbent-assay (ELISA), and by light and electron microscopy using immunocytological methods. During the exponential growth phase, mucins were accumulated in the cytoplasm of cells and slowly exocytosed. In contrast, there was enhanced exocytosis of mucins during the stationary phase when the cells were well-polarized.

Effects of ketoconazole on the proliferation and cell cycle of human cancer cell lines.

The growth-inhibitory effects of ketoconazole, an antifungal agent which inhibits arachidonic acid lipoxygenases and cytochrome P-450 enzymes, were tested in human colon and breast cancer cell lines. In the serum independent HT29-S-B6 colon cell clone, ketoconazole reduced cell proliferation and [3H]thymidine incorporation in a dose-dependent fashion, with a 50% inhibitory concentration of approximately 2.5 microM.

Proliferation of the human colon carcinoma cell line HT29: autocrine growth and deregulated expression of the c-myc oncogene.

Human colon adenocarcinoma cell (line HT29) are able to proliferate in a defined (serum-free) medium containing no added growth factors; in such conditions, their doubling time is 3 to 4 days (on serum-coated dishes) or 2 to 3 days (on an autologous extracellular matrix) compared with 1 day in the presence of fetal calf serum. In the presence of suramin, a polyanion disrupting the binding of growth factors to their receptors, the incorporation of [3H]thymidine in serum-free cultures is reduced (27.0 +/- 2.

Development of insulin and epidermal growth factor receptors during the differentiation of rat preadipocytes in primary culture.

An homogeneous cell population isolated from the inguinal tissue of 3-day-old rats is able to proliferate in primary culture. In the presence of a physiological concentration of insulin (1.5 nM) it converts into cells exhibiting the morphology and the biochemical characteristics of adipocytes.

Insulin binding in epithelial cells isolated from human gallbladder.

The binding of 125I-insulin was studied in epithelial cells isolated from human gallbladder. Kinetic studies at 22 degrees C showed that binding of 125I-insulin to gallbladder cells was rapid (maximum 1 h.) and reversible.

Characterization and repartition of epidermal growth factor-urogastrone receptors in gastric glands isolated from young and adult guinea pigs.

Physiological studies indicate that epidermal growth factor-urogastrone (EGF) acts on stomach epithelium as mitogen and modulator of acid secretion. Here, we studied the binding of 125I-EGF to gastric glands isolated from the guinea-pig fundus (acid-secreting part) and antrum. At 20 degrees C, the association of 125I-EGF to gastric glands was time-dependent (plateau at 90 min) and reversible (75-85% dissociation in 1 h).

Histamine and VIP interactions with receptor-cyclic AMP systems in the human gastric cancer cell line HGT-1.

In HGT-1 cells incubated at 20 degrees C for 15 min with 1 mM 3-isobutyl-1-methylxanthine (IBMX), histamine (10(-4)M) increased basal cAMP levels from 2.12 +/- 0.14 to 22.