TY - JOUR
T1 - The epigenetic reprogramming of poorly aggressive melanoma cells by a metastatic microenvironment
AU - Seftor, Elisabeth A.
AU - Meltzer, P. S.
AU - Kirschmann, D. A.
AU - Margaryan, N. V.
AU - Seftor, Richard E.B.
AU - Hendrix, Mary J.C.
PY - 2006
Y1 - 2006
N2 - A dynamic, complex relationship exists between tumor cells and their microenvironment, which plays a pivotal role in cancer progression, yet remains poorly understood. Particularly perplexing is the finding that aggressive melanoma cells express genes associated with multiple cellular phenotypes, in addition to their ability to form vasculogenic-like networks in three-dimensional matrix - called vasculogenic mimicry, which is illustrative of tumor cell plasticity. This study addressed the unique epigenetic effect of the microenvironment of aggressive melanoma cells on the behavior of poorly aggressive melanoma cells exposed to it. The data show significant changes in the global gene expression of the cells exposed to 3-D matrices preconditioned by aggressive melanoma cells, including the acquisition of a vasculogenic cell phenotype, upregulation of ECM remodeling genes, and increased invasive ability - indicative of an epigenetic, microenvironment-induced reprogramming of poorly aggressive melanoma cells. However, this epigenetic effect was completely abrogated when a highly cross-linked collagen matrix was used, which could not be remodeled by the aggressive melanoma cells. These findings offer an unique perspective of the inductive properties associated with an aggressive melanoma microenvironment that might provide new insights into the epigenetic regulation of tumor cell plasticity and differentiation, as well as mechanisms that could be targeted for novel therapeutic strategies.
AB - A dynamic, complex relationship exists between tumor cells and their microenvironment, which plays a pivotal role in cancer progression, yet remains poorly understood. Particularly perplexing is the finding that aggressive melanoma cells express genes associated with multiple cellular phenotypes, in addition to their ability to form vasculogenic-like networks in three-dimensional matrix - called vasculogenic mimicry, which is illustrative of tumor cell plasticity. This study addressed the unique epigenetic effect of the microenvironment of aggressive melanoma cells on the behavior of poorly aggressive melanoma cells exposed to it. The data show significant changes in the global gene expression of the cells exposed to 3-D matrices preconditioned by aggressive melanoma cells, including the acquisition of a vasculogenic cell phenotype, upregulation of ECM remodeling genes, and increased invasive ability - indicative of an epigenetic, microenvironment-induced reprogramming of poorly aggressive melanoma cells. However, this epigenetic effect was completely abrogated when a highly cross-linked collagen matrix was used, which could not be remodeled by the aggressive melanoma cells. These findings offer an unique perspective of the inductive properties associated with an aggressive melanoma microenvironment that might provide new insights into the epigenetic regulation of tumor cell plasticity and differentiation, as well as mechanisms that could be targeted for novel therapeutic strategies.
KW - 3-dimensional matrix
KW - Epigenetic
KW - Melanoma
KW - Plasticity
KW - Tumor microenvironment
KW - Vasculogenic mimicry
UR - http://www.scopus.com/inward/record.url?scp=33748342943&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748342943&partnerID=8YFLogxK
U2 - 10.1111/j.1582-4934.2006.tb00299.x
DO - 10.1111/j.1582-4934.2006.tb00299.x
M3 - Article
C2 - 16563230
AN - SCOPUS:33748342943
SN - 1582-1838
VL - 10
SP - 174
EP - 196
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 1
ER -