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Tumor cell plasticity and angiogenesis in human melanomas


Mihic-Probst, Daniela; Ikenberg, Kristian; Tinguely, Marianne; Schraml, Peter; Behnke, Silvia; Seifert, Burkhardt; Civenni, Gianluca; Sommer, Lukas; Moch, Holger; Dummer, Reinhard (2012). Tumor cell plasticity and angiogenesis in human melanomas. PLoS ONE, 7(3):e33571.

Abstract

Recent molecular studies provide evidence for a significant transcriptional plasticity of tumor cell subpopulations that facilitate an active contribution to tumor vasculature. This feature is accompanied by morphological changes both in vitro and in vivo. Herein, we investigated the morphological plasticity of tumor cells with special focus on vasculogenic mimicry and neovascularisation in human melanoma and mouse xenografts of human melanoma cell lines. In melanoma xenograft experiments, different vessel markers and green fluorescent protein expression were used to show how melanoma cells contribute to neovascularization. Additionally, we analyzed neovascularization in 49 primary melanomas and 175 melanoma metastases using immunostaining for blood (CD34) and lymphatic (D2-40) vessel-specific markers. We found significantly more lymphatic vessels in primary melanomas than in melanoma metastases (p<0.0001). In contrast to the near absence of lymphatic vessels within metastases, we found extensive blood micro-neovascularization. Blood micro-neovascularization was absent in micro metastases (less than 2 mm). A significant inverse correlation between Glut-1 expression (implying local hypoxia) and the presence of microvessels indicates their functional activity as blood vessels (p<0.0001). We suggest that the hypoxic microenvironment in metastases contributes to a phenotype switch allowing melanoma cells to physically contribute to blood vessel formation.

Recent molecular studies provide evidence for a significant transcriptional plasticity of tumor cell subpopulations that facilitate an active contribution to tumor vasculature. This feature is accompanied by morphological changes both in vitro and in vivo. Herein, we investigated the morphological plasticity of tumor cells with special focus on vasculogenic mimicry and neovascularisation in human melanoma and mouse xenografts of human melanoma cell lines. In melanoma xenograft experiments, different vessel markers and green fluorescent protein expression were used to show how melanoma cells contribute to neovascularization. Additionally, we analyzed neovascularization in 49 primary melanomas and 175 melanoma metastases using immunostaining for blood (CD34) and lymphatic (D2-40) vessel-specific markers. We found significantly more lymphatic vessels in primary melanomas than in melanoma metastases (p<0.0001). In contrast to the near absence of lymphatic vessels within metastases, we found extensive blood micro-neovascularization. Blood micro-neovascularization was absent in micro metastases (less than 2 mm). A significant inverse correlation between Glut-1 expression (implying local hypoxia) and the presence of microvessels indicates their functional activity as blood vessels (p<0.0001). We suggest that the hypoxic microenvironment in metastases contributes to a phenotype switch allowing melanoma cells to physically contribute to blood vessel formation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:19 Apr 2012 07:00
Last Modified:17 Aug 2016 08:30
Publisher:Public Library of Science (PLoS)
ISSN:1932-6203
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1371/journal.pone.0033571
PubMed ID:22442699
Permanent URL: https://doi.org/10.5167/uzh-61605

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