Zusammenfassung
Ein wichtiger Aspekt der Tumorentwicklung im Dickdarm ist progressive Deregulation des Zell Wachstums. Die schrittweise Veränderung der Wachstumsregulation spiegelt sich auch in Wachstumsverhalten und Überlebensfähigkeit der Zellen in vitro wider. Tumorzellen besitzen längere Überlebensfähigkeit, autokrine Wachstumsstimulation, erhöhte Sensitivität für exogene mitogene Signale und verminderte Sensititvität für wachstumshemmende Signale als normale Epithelzellen. Dennoch können auch normale und frühe prämalignen Zellen unter geeigneten Bedingungen für 2 oder mehr Wochen in Kultur gehalten und untersucht werden. Dazu sind krypten-assoziierte Fibroblasten als Unterlage und ein definiertes Medium notwendig. Aufbauend auf diesen Beobachtungen haben wir ein Primärkultur-Modell entwickelt, das zur Untersuchung der zugrundeliegenden Mechanismen und zur Bestimmung tumorfördernder und tumorhemmender Substanzen herangezogen werden kann.
Summary
Colorectal cancer is a disease of progressive deregulation of growth. Stepwise alterations of growth control is also reflected in the growth and survival of epithelial cells in vitro. Tumor cells have extended life spans, autocrine growth stimulation, enhanced sensitivity to exogenous growth signals and decreased sensitivity to growth inhibition as compared to normal epithelial cells. However, using pericryptal fibroblasts and a defined medium the cultivation of normal and early premalignant cells for up to 2 weeks is possible. Based on these observation we have developed a primary culture model that allowes investigation of the underlying growth control mechanisms and the effets of tumor enhancing and tumorinhibiting substances.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
Literatur
Bedi A., Pasricha P.J., Akhtara J ., Barber J.P., Bedi G.C., Giardiello F.M., Zehnbauer B.A ., Hamilton S.R., Jones R.J.,Inhibition of apoptosis during development of colorectal cancer, Cancer Research, 55, 1811–1816, 1995
Buset M., Winawer S., Friedman E.,Defining conditions to promote the attachment of adult human colonic epithelial cells, In Vitro Cell Developmental Biology, 23 403–412, 1987
Coffey R.J. JR., Shipley G.D., Moses H.L.,Production of transforming growth factors by human colon cancer lines, Cancer Research, 46, 1164–1169, 1986
Deschner E.E. and Lipkin M.,Proliferative patterns in colonic mucosa in familial polyposis, Cancer, 35, 413–418, 1975
Doll R. and Peto R.,The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today, Journal of the National Cancer Institute, 66, 1191, 1981
Fearon E.R. and Vogelstein B.A., genetic model for colorectal tumorigenesis, Cell, 61, 759–767,1990
Friedman E., Isaksson P., Rafter J., Marian B., Winawer S., Newmark H.,Fecal diglycerides as selective endogenous mitogens for premalignant and malignant human colonic epithelial cells, Cancer Research, 49, 544–548, 1989a
Friedman E., Lipkin M., Winawer S., Buset M., Newmark H.,Heterogeneity in the response of familial polyposis epithelial cells and adenomas to increasing levels of calcium in vitro, Cancer, 63, 2486–2491, 1989b
Friedman E., Urmacher C., Winawer SA.,model for human colon Carcinoma evolution based on the differential response of cultured preneoplastic, premalignant, and malignant cells to 12-0- tetradecanoylphorbol-13-acetate, Cancer Research, 44, 1568–1578, 1984
Hsu S., Huang F., Hafez M., Winawer S., Friedman E.,Colon cancer cells switch their response to transforming growth factor beta 1 with tumor progression, Cell Growth and Differntiation, 5, 267– 275,1994
Kahl-Rainer P., Karner Hanusch J., Weiss W., Marian B.,Five of six protein kinase C isoenzymes present in normal mucosa show reduced protein levels during tumor development in the human colon, Carcinogenesis, 15, 779–782, 1994
Kahl-Rainer P., Sedivy R., Marian B.,Protein kinase C tissue location in human colonic tumors suggests a role for adenoma growth control, Gastroenterology 110, 1753–1759, 1996
Karnes W.E. JR., Walsh J.H., Wu S.V., Kim R.S., Martin M.G., Wong H.C., Mendelsohn J., Park J.G., Cuttitta F.,Autonomous proliferation of colon cancer cells that coexpress transforming growth factor alpha and its receptor. Variable effects of receptor-blocking antibody, Gastroenterology, 102,474–458, 1992
Lee H., Ghose-Dastidar J., Winawer S., Friedman E.,Signal transduction through extracellular signal-regulated kinase-like pp57 blocked in differentiated cells having low protein kinase C beta activity, Journal of Biological Chemistry, 268, 5255–5263, 1993
Manning A., Williams A.C., Game S.M., Paraskeva C.,Differential sensitivity of human colonic adenoma and Carcinoma cells to transforming growth factor ß (TGFß): conversion of an adenoma cell line to a tumorigenic phenotype is accompanied by a reduced response to the inhibitory effects of TGFß, Oncogene, 6, 1471–1476, 1991
Marian B., Harvey S., Infante D., Markus G., Winawer S., Friedman E.,Urokinase secretion f r om human colon carcinomas induced by endogenous diglycerides, Cancer Research, 50, 2245–2250, 1990
Markowitz S.D., Molkentin K., Gerbic C., Jackson J., Stellato T., Willson J.K.,Growth Stimulation by coexpression of transforming growth factor-alpha and epidermal growth factorreceptor in normal and adenomatous human colon epithelium, Journal of Clinical Investigation, 86, 356–62, 1990
Mclellan E.A., Medline A., Bird R.P.,Sequential analyses of the growth and morphological characteristics of aberrant crypt fori: putative preneoplastic lesions, Cancer Research, 51, 5270–5274, 1991
Pretlow T.P., Ma O.R., Pretlow T.G., Stellato T.A.,Aberrant crypts in human colonic mucosa: putative preneoplastic lesions, Journal of Cellular Biochemistry, Supplement, 16g, 55–62, 1992
Reddy B.S.,Dietary fat and colon cancer: animal model studies, Lipids, 27, 807–813, 1992
Schörkhuber M., Karner-Hanusch J., Sedivy R., Ellinger A., Armbruster C., Schultehermann R.,Marian B.,Survival of normal colonic epithelial cells is prolonged by coculture with rat embryo colonic fibroblasts, Cell Biology and Toxicology, 1997
Stopera S.A. and Bird R . P., Expression of ras oncogene mRNA and protein in aberrant crypt foci, Carcinogenesis, 13, 1863–1868, 1992
Stopera S.A., Davie J.R, Bird R . P., Colonic aberrant crypt foci are associated with increased expression of c-fos: the possible role of modified c-fos expression in preneoplastic lesions in colon cancer, Carcinogenesis, 13, 573–578, 1992
Vogel V.G. and Mcpherson R . S., Dietary epidemiology of colon cancer, Hematological Oncological Clinic North America, 3, 35–63, 1989
Weinstein I.B., The role of protein kinase C in growth control and the concept of carcinogenesis as a progressive disorder in signal transduction. Advances in Second Messenger Phosphoprotein Research, 24, 307–16, 1990
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer-Verlag/Wien
About this paper
Cite this paper
Marian, B. (2000). Entwicklung kolorektaler Karzinome: Das Wachstumsverhalten von Epithelzellen in Primärkultur spiegelt Regulationsmechanismen in vivo wider. In: Schöffl, H., et al. Forschung ohne Tierversuche 2000. Ersatz- und Ergänzungsmethoden zu Tierversuchen. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6760-1_22
Download citation
DOI: https://doi.org/10.1007/978-3-7091-6760-1_22
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-83046-8
Online ISBN: 978-3-7091-6760-1
eBook Packages: Springer Book Archive