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Stellenwert der Zellkulturmodelle in kutaner Tumorbiologie

Teil I: Zelllinien tumorigen transformierter Zellen

Relevance of cell culture models in cutaneous tumour biology

Part I: Tumour cell lines

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Zusammenfassung

Plattenepithelkarzinome und Basalkarzinome der Haut sowie das maligne Melanom entstehen als Ergebnis eines vielstufigen Prozesses, bei dem sich genetische und epigenetische Veränderungen in den betroffenen Zellen anhäufen. Ein Einblick in die Biologie menschlicher Tumoren ist eine wesentliche Bedingung für die Entwicklung effektiver Therapieverfahren. Zellkulturmodelle stellen ein fruchtbares experimentelles System dar. Das Ausmaß der tumorigenen Transformation kann präzise definiert werden. Tumorzelllinien zeigen ähnliche funktionelle Hierarchien wie Tumoren bzw. Gewebe in vivo und können zu einer wichtigen Quelle für die Aufreinigung und Charakterisierung minoritärer Zellpopulationen, wie z. B. Tumorstammzellen, werden. In Serien von klonal verwandten Zelllinien können die einzelnen Komponenten des tumorigenen Phänotyps weitgehend separiert werden. Dies ergibt Einblicke in die schrittweise Entwicklung der klinisch relevanten Parameter wie Tumorigenität oder metastatische Kompetenz. Zudem kann diese phänotypische Entwicklung mit den Veränderungen in der Struktur und Expression des Genoms der Zellen korreliert werden. Während für die meisten Studien humane tumorigen transformierte Zelllinien bevorzugt werden, sind für spezielle Fragestellungen Tumorzelllinien tierischer Abstammung unentbehrlich. Bei der Auswertung der Zellkulturexperimente muss man sich der Möglichkeit eines Artefakts bewusst sein und alle Ergebnisse mit komplexen Zellkultur- oder tierischen Modellen und klinischen Proben konfrontieren.

Abstract

Cutaneous squamous cell carcinoma, basal cell carcinoma and melanoma, much like all other human solid tumors, result from a multi-step process in which genetic and epigenetic changes accumulate in the affected cells. Insight into the biology of human tumors is a requirement for developing effective therapies. Cell culture models are a very valuable experimental system. The degree of tumorigenic transformation can be precisely defined. Tumor cell lines display similar functional hierarchy as tumors or tissues in vivo and can, consequently, provide a crucial source of minor cell subsets, like tumor stem cells. Progression series of clonally related cell lines offer the opportunity to follow the process of sequential acquisition of transformation-related traits up to the development of properties with direct clinical equivalents, like tumorigenicity and metastatic competence. These phenotypical changes can be directly correlated with changes at the genome level, concerning both gene structure and expression. While for most studies, human transformed cell lines are the model of choice, there are questions for which animal cell lines are strongly preferred, such as interactions between the tumor and the immune system. To properly interpret the results of all experiments with classical two-dimensional cell culture, a possible danger of artifacts due to grossly unnatural environment must be constantly taken into account. It is thus obligatory to confirm any such result with other experimental models like complex three-dimensional culture models or experimental animals, and with clinical samples.

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Abb. 1

Abbreviations

ABC:

ATP-binding casette

BCRP:

breast cancer resistance protein

GFP:

green fluorescent protein

MAPK:

mitogen-activated protein kinase

MHC:

major histocompatibility complex

MM:

metastatic melanoma

PDGF:

platelet-derived growth factor

RGP:

radial growth phase

SCID:

severe combined immunodeficiency

SCID/NOD:

severe combined immunodeficiency/non-obese diabetic

SP:

side population

VGP:

vertical growth phase

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Danksagung

Die Autoren sind Herrn Univ.-Prof. Dr. Wolfgang A. Schulz und einem anonymen Gutachter für das kritische Lesen des Manuskripts und Frau Prof. Mary Hendrix, Frau Dr. Angela Hess, Frau Dr. Denisa Kacerovska, Herrn Dr. Josef Bizik und Herrn Dr. Jan Peychl für die Überlassung von Originalabbildungen dankbar. PD Jiri Hatina wurde durch die DAAD-Gastdozentur an der Heinrich-Heine Universität Düsseldorf unterstützt.

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  1. Forschungslabor der Urologischen Klinik, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland

    J. Hatina

  2. Institut für Biologie, Karlsuniversität Prag, Medizinische Fakultät zu Pilsen, Karlovarská 48, 30166, Plzen, Tschechische Republik

    J. Hatina

  3. Klinik und Poliklinik für Dermatologie und Allergologie der Ludwig-Maximilians-Universität München, München, Deutschland

    T. Ruzicka

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Hatina, J., Ruzicka, T. Stellenwert der Zellkulturmodelle in kutaner Tumorbiologie. Hautarzt 59, 36–45 (2008). https://doi.org/10.1007/s00105-007-1436-4

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