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Title: Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells

Abstract

Prominin-1 (CD133) is the first identified gene of a novel class of pentaspan membrane glycoproteins. It is expressed by various epithelial and non-epithelial cells, and notably by stem and cancer stem cells. In non-cancerous cells such as neuro-epithelial and hematopoietic stem cells, prominin-1 is selectively concentrated in plasma membrane protrusions, and released into the extracellular milieu in association with small vesicles. Previously, we demonstrated that prominin-1 contributes to melanoma cells pro-metastatic properties and suggested that it may constitute a molecular target to prevent prominin-1-expressing melanomas from colonizing and growing in lymph nodes and distant organs. Here, we report that three distinct pools of prominin-1 co-exist in cultures of human FEMX-I metastatic melanoma. Morphologically, in addition to the plasma membrane localization, prominin-1 is found within the intracellular compartments, (e.g., Golgi apparatus) and in association with extracellular membrane vesicles. The latter prominin-1–positive structures appeared in three sizes (small, ≤40 nm; intermediates ∼40–80 nm, and large, >80 nm). Functionally, the down-regulation of prominin-1 in FEMX-I cells resulted in a significant reduction of number of lipid droplets as observed by coherent anti-Stokes Raman scattering image analysis and Oil red O staining, and surprisingly in a decrease in the nuclear localization of beta-catenin, a surrogatemore » marker of Wnt activation. Moreover, the T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity was 2 to 4 times higher in parental than in prominin-1-knockdown cells. Collectively, our results point to Wnt signaling and/or release of prominin-1–containing membrane vesicles as mediators of the pro-metastatic activity of prominin-1 in FEMX-I melanoma. - Highlights: ► First report of release of prominin-1–containing microvesicles from cancer cells. ► Pro-metastatic role of prominin-1–containing microvesicles in FEMX-I melanoma. ► Down-regulation of prominin-1 results in decreased nuclear localization of β-catenin. ► Wnt signaling as mediator of the pro-metastatic activity of prominin-1.« less

Authors:
 [1];  [2]; ;  [1];  [3];  [1];  [2];  [1];  [2];  [2];  [4];  [5];  [1];  [2]
  1. Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States)
  2. (United States)
  3. Nevada Cancer Institute, Las Vegas, NV 89135 (United States)
  4. Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden (Germany)
  5. Tissue Engineering Laboratories (BIOTEC) and DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Tatzberg 47–49, 01307 Dresden, Germany Technische Universitat Dresden, Dresden (Germany)
Publication Date:
OSTI Identifier:
22278220
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 319; Journal Issue: 6; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 60 APPLIED LIFE SCIENCES; GLYCOPROTEINS; GOLGI COMPLEXES; IMAGE PROCESSING; LYMPH NODES; MELANOMAS; MEMBRANES; METASTASES; STEM CELLS

Citation Formats

Rappa, Germana, College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104, Mercapide, Javier, Anzanello, Fabio, Le, Thuc T., Johlfs, Mary G., Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104, Fiscus, Ronald R., College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104, Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104, Wilsch-Bräuninger, Michaela, Corbeil, Denis, Lorico, Aurelio, E-mail: alorico@roseman.edu, and College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104. Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells. United States: N. p., 2013. Web. doi:10.1016/J.YEXCR.2013.01.003.
Rappa, Germana, College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104, Mercapide, Javier, Anzanello, Fabio, Le, Thuc T., Johlfs, Mary G., Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104, Fiscus, Ronald R., College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104, Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104, Wilsch-Bräuninger, Michaela, Corbeil, Denis, Lorico, Aurelio, E-mail: alorico@roseman.edu, & College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104. Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells. United States. doi:10.1016/J.YEXCR.2013.01.003.
Rappa, Germana, College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104, Mercapide, Javier, Anzanello, Fabio, Le, Thuc T., Johlfs, Mary G., Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104, Fiscus, Ronald R., College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104, Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104, Wilsch-Bräuninger, Michaela, Corbeil, Denis, Lorico, Aurelio, E-mail: alorico@roseman.edu, and College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104. Mon . "Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells". United States. doi:10.1016/J.YEXCR.2013.01.003.
@article{osti_22278220,
title = {Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells},
author = {Rappa, Germana and College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 and Mercapide, Javier and Anzanello, Fabio and Le, Thuc T. and Johlfs, Mary G. and Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 and Fiscus, Ronald R. and College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 and Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 and Wilsch-Bräuninger, Michaela and Corbeil, Denis and Lorico, Aurelio, E-mail: alorico@roseman.edu and College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104},
abstractNote = {Prominin-1 (CD133) is the first identified gene of a novel class of pentaspan membrane glycoproteins. It is expressed by various epithelial and non-epithelial cells, and notably by stem and cancer stem cells. In non-cancerous cells such as neuro-epithelial and hematopoietic stem cells, prominin-1 is selectively concentrated in plasma membrane protrusions, and released into the extracellular milieu in association with small vesicles. Previously, we demonstrated that prominin-1 contributes to melanoma cells pro-metastatic properties and suggested that it may constitute a molecular target to prevent prominin-1-expressing melanomas from colonizing and growing in lymph nodes and distant organs. Here, we report that three distinct pools of prominin-1 co-exist in cultures of human FEMX-I metastatic melanoma. Morphologically, in addition to the plasma membrane localization, prominin-1 is found within the intracellular compartments, (e.g., Golgi apparatus) and in association with extracellular membrane vesicles. The latter prominin-1–positive structures appeared in three sizes (small, ≤40 nm; intermediates ∼40–80 nm, and large, >80 nm). Functionally, the down-regulation of prominin-1 in FEMX-I cells resulted in a significant reduction of number of lipid droplets as observed by coherent anti-Stokes Raman scattering image analysis and Oil red O staining, and surprisingly in a decrease in the nuclear localization of beta-catenin, a surrogate marker of Wnt activation. Moreover, the T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity was 2 to 4 times higher in parental than in prominin-1-knockdown cells. Collectively, our results point to Wnt signaling and/or release of prominin-1–containing membrane vesicles as mediators of the pro-metastatic activity of prominin-1 in FEMX-I melanoma. - Highlights: ► First report of release of prominin-1–containing microvesicles from cancer cells. ► Pro-metastatic role of prominin-1–containing microvesicles in FEMX-I melanoma. ► Down-regulation of prominin-1 results in decreased nuclear localization of β-catenin. ► Wnt signaling as mediator of the pro-metastatic activity of prominin-1.},
doi = {10.1016/J.YEXCR.2013.01.003},
journal = {Experimental Cell Research},
number = 6,
volume = 319,
place = {United States},
year = {Mon Apr 01 00:00:00 EDT 2013},
month = {Mon Apr 01 00:00:00 EDT 2013}
}