Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-13926
Hoek, K S; Eichhoff, O M; Schlegel, N C; Döbbeling, U; Kobert, N; Schaerer, L; Hemmi, S; Dummer, R (2008). In vivo switching of human melanoma cells between proliferative and invasive states. Cancer Research, 68(3):650-656.
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Metastatic melanoma represents a complex and heterogeneous disease for which there are no therapies to improve patient survival. Recent expression profiling of melanoma cell lines identified two transcription signatures, respectively, corresponding with proliferative and invasive cellular phenotypes. A model derived from these findings predicts that in vivo melanoma cells may switch between these states. Here, DNA microarray-characterized cell lines were subjected to in vitro characterization before s.c. injection into immunocompromised mice. Tumor growth rates were measured and postexcision samples were assessed by immunohistochemistry to identify invasive and proliferative signature cells. In vitro tests showed that proliferative signature melanoma cells are faster growing but less motile than invasive signature cells. In vivo proliferative signature cells initiated tumor growth in 14 +/- 3 days postinjection. By comparison, invasive signature cells required a significantly longer (P < 0.001) period of 59 +/- 11 days. Immunohistochemistry showed that regardless of the seed cell signature, tumors showed evidence for both proliferative and invasive cell types. Furthermore, proliferative signature cell types were detected most frequently in the peripheral margin of growing tumors. These data indicate that melanoma cells undergo transcriptional signature switching in vivo likely regulated by local microenvironmental conditions. Our findings challenge previous models of melanoma progression that evoke one-way changes in gene expression. We present a new model for melanoma progression that accounts for transcription signature plasticity and provides a more rational context for explaining observed melanoma biology.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic|
07 Faculty of Science > Institute of Molecular Life Sciences
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||18 Feb 2009 16:58|
|Last Modified:||27 Nov 2013 21:35|
|Publisher:||American Association for Cancer Research|
|Citations:||Web of Science®. Times cited: 101|
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