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M Bowman

Publications and source records attributed to M Bowman.

At least 55 records · Page 3Linked to original sources

Distribution of developmental markers in rat mammary tumors induced by N-nitrosomethylurea.

We have examined the distribution of immunological markers in 55 intraductal carcinomas induced in rats by N-nitrosomethylurea using several different regimens of carcinogen treatment. The goal was to determine the possible relationship of the marker distribution to those existing at various stages of development of the mammary gland. We have also examined two passage lines in syngeneic rats derived from two of the tumors. The distribution of markers was not affected by the regimen of administration. The primary tumors were found to maintain the general topography of mammary ducts but with infoldings of the basal layer without accompanying stroma. We attribute this to an abnormal expression of the tendency of basal cells to migrate towards the lumen to generate luminal cells. The distribution of markers in the tumors was evaluated by identifying 13 special features of distribution that are common in tumors, using all-or-none criteria. The distribution of these features bears out the high heterogeneity of tumors in which the various features vary in a seemingly independent way. There is also heterogeneity within tumors, adjacent nodes often having different marker distributions. The distribution of the markers is related to that found in the early stages of mammary development. Because of this characteristic and of the fact that the tumors contain both basal and luminal cells, they must originate from multipotent cells, probably the stem cells present in end buds and ducts as already proposed by other work. As they develop, the tumors can both differentiate towards the adult type and dedifferentiate towards a fetal type. Of the two transplanted lines one retained the same general features of primary tumors in several passages, whereas the other evolved into a fusiform cell type with a marker distribution not seen at any stage of mammary development. Foci of similar cells were already present in the primary tumor, suggesting that the tendency to progress was already determined at an early stage. The fusiform cells are similar and probably equivalent to the fusiform cells that arise in vitro in cultures of rat mammary cancers.

Animals↗

Two monoclonal antibodies selective for human mammary carcinoma.

Mouse myeloma cells were fused with spleen cells from BALB/c mice immunized with the MCF-7 human mammary carcinoma cell line. Among hybridomas, two (3B18 and 15A8) were selected and cloned. Hybridoma 3B18 produces kappa-IgG1 antibodies that react with a cytoplasmic component of MCF-7 cells. In immunoperoxidase assays, 3B18 reacts with 27 of 31 specimens of human mammary carcinoma. It reacts most consistently with poorly differentiated and infiltrating ductal breast cancers, but it also reacts with isolated cells in 3 of 5 benign mammary pathological lesions with a variable distribution. The antibody does not react with normal mammary epithelium. It does not react with any normal human tissues, and it reacts with only one of 19 other cancers tested. Hybridoma 15A8 produces kappa-IgG1 antibodies that react with the surface membranes of the cells of two human breast cancer cell lines but not with a human fibroblast cell line. In immunoperoxidase assays, the antibody reacted with 28 out of 31 human mammary carcinomas. The antibody also reacts more weakly with normal human epithelial cells of breast, renal proximal tubule, skin, esophagus, and salivary gland, but no other normal tissue. The antibody was unreactive with 14 of 18 other malignant tissues tested. Since 3B18 and 15A8 detect antigens found predominantly in human mammary carcinomas and, possibly, distinguish overlapping categories of human mammary carcinomas, they may prove useful in determining the cellular lineage from which human mammary carcinomas arise, or they may have other clinical applications in breast cancer.

Antibodies, Monoclonal↗

Microvillin: a 200-kilodalton protein in microvilli of rat mammary cells detected by a monoclonal antibody.

We have isolated a monoclonal antibody that was raised against rat mammary tumor cells. The antibody stains the lumenal edge of mammary duct epithelial cells. It immunoprecipitates a 200-kilodalton nonglycosylated, nonphosphorylated protein, which, by immunofluorescence and electron microscopy, can be localized in microvilli. In addition to microvilli of mammary ducts, this monoclonal antibody stains microvilli of the salivary ducts and of the renal nephron. It does not stain the microvilli of the intestinal brush border and shows a different tissue distribution than previously described proteins of this microvillus. We propose the name microvillin to distinguish the protein from other microvillar proteins. The presence of the protein distinguishes two classes of microvilli that are present in cells with possibly different transport functions.

Animals↗

Lumen formation and redistribution of inframembranous proteins during differentiation of ducts in the rat mammary gland.

During the development of the rat mammary gland, ducts are formed from end-buds, which contain the stem cells. In this process a lumen is formed in the semisolid mass of the end-bud, and the cells acquire polarity. We have studied this process by following the localization of three inframembranous proteins present in the cells of both end-buds and ducts: microvillin, the microvillar protein p80, and the desmosomal plaque protein p205. We find that the development of ducts is accompanied by a redistribution of these proteins, which in immature parts of the end-buds are found together in the cell. Microvillin and p80 go together to the apical pole of the cells, in contact with the lumen, whereas p205 goes to the basal surface, in contact with cells of the myoepithelial lineage. The acquisition of polarity occurs at the same time as a lumen begins to form by local gaps between cells. It seems likely that the redistribution of the inframembraneous proteins is the consequence of the localization of surface glycoproteins that affect in opposite ways the adhesion between the cells.

Animals↗

Developmental regulation of cytokeratins in cells of the rat mammary gland studied with monoclonal antibodies.

We have isolated two monoclonal antibodies to cytokeratins and determined their cell specificities. They display interesting localization within the rat mammary gland. One (1A10) shows specificity for myoepithelial cells; the other (24B42) is specific for lumenal cells at various stages of development. These two monoclonal antibodies and three others to cytokeratin previously isolated were used in conjunction with antibodies to myosin and collagen IV to confirm and extend our previous findings on epithelial cell types and development within the mammary gland.

Aging↗

Epithelial cell types and their evolution in the rat mammary gland determined by immunological markers.

We have used immunological reagents for characterizing epithelial cell types in the adult rat mammary gland. Some were sera against purified proteins; others were monoclonal antibodies to mammary cells. On the basis of marker distribution we have identified 10 different cell types. We have established the developmental connection between these types by adopting the principle that cells displaying the same markers are directly related to each other. The results concur with those previously obtained by studying the growth response of mammary cells to the hormonal changes of the estrus cycle.

Animals↗

Functional changes of intermediate filaments in fibroblastic cells revealed by a monoclonal antibody.

We describe reversible changes of intermediate filaments of fibroblastic cells associated with changes in the functional state of the cells. The changes are revealed by comparing the immunofluorescence patterns given by a monoclonal antibody and a polyclonal serum, both recognizing vimentin. The state of the filaments depends on culture density; this effect cannot be attributed to the nutritional state of the cells, their growth rate, or substances released into the medium. It seems to depend mainly on the aggregation of filaments during strong cell movements. The possible significance of these findings for the functional role of intermediate filaments is discussed.

Animals↗

Generation of fibroblast-like cells from cloned epithelial mammary cells in vitro: a possible new cell type.

We have isolated clonal cell lines from a nitrosomethylurea-induced mammary tumor in Wistar--Furth rats. The epithelial-like cells of these lines give rise to fibroblast-like cells. A study of several markers showed that the epithelial-like cells are similar to epithelial mammary cells. The fibroblastic cells, however, were similar to stromal cells, except for the production of collagen IV. The events occurring in these cultures are identical to those observed in previously isolated mammary cultures [Bennett, D. C., Peachey, L. A., Durbin, H. & Rudland, P. S. (1976) Cell 15, 283--298], suggesting their generality. The fibroblast-like cells generated in culture may be a hitherto unrecognized type of mammary cell.

Animals↗

Learning to teach.

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Education, Nursing↗