Aggressive melanoma cells escape from BMP7-mediated autocrine growth inhibition through coordinated Noggin upregulation

Mei-Yu Hsu; Sherry A Rovinsky; Chiou-Yan Lai; Shadi Qasem; Xiaoming Liu; Joan How; John F Engelhardt; George F Murphy

doi:10.1038/labinvest.2008.55

Back

Aggressive melanoma cells escape from BMP7-mediated autocrine growth inhibition through coordinated Noggin upregulation

Journal article

Open access

Peer reviewed

Aggressive melanoma cells escape from BMP7-mediated autocrine growth inhibition through coordinated Noggin upregulation

Mei-Yu Hsu, Sherry A Rovinsky, Chiou-Yan Lai, Shadi Qasem, Xiaoming Liu, Joan How, John F Engelhardt and George F Murphy

Laboratory investigation, Vol.88(8), pp.842-855

08/2008

DOI: 10.1038/labinvest.2008.55

PMCID: PMC2676927

PMID: 18560367

Files and links (1)

url

https://doi.org/10.1038/labinvest.2008.55View

Published (Version of record) Open Access

Abstract

Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily responsible for mediating a diverse array of cellular functions both during embryogenesis and in adult life. Previously, we reported that upregulation of BMP7 in human melanoma correlates with tumor progression. However, melanoma cells are either inhibited by or become resistant to BMP7 as a function of tumor progression, with normal melanocytes being most susceptible. Herein, real-time quantitative reverse transcriptase-polymerase chain reactions and western blotting revealed that the expression of BMP antagonist, Noggin, correlates with resistance to BMP7 in advanced melanoma cells. To test the hypothesis that coordinated upregulation of Noggin protects advanced melanoma cells from autocrine inhibition by BMP7, functional expression of Noggin in susceptible melanoma cells was achieved by adenoviral gene transfer. The Noggin-overexpressing cells exhibited a growth advantage in response to subsequent BMP7 transduction in vitro under anchorage-dependent and -independent conditions, in three-dimensional skin reconstructs, as well as in vivo in severe combined immunodeficient mice. In concordance, Noggin knockdown by lentiviral shRNA confers sensitivity to BMP7-induced growth inhibition in advanced melanoma cells. Our findings suggest that, like TGF-beta, BMP7 acts as an autocrine growth inhibitor in melanocytic cells, and that advanced melanoma cells may escape from BMP7-induced inhibition through concomitant aberrant expression of Noggin.

Adenoviridae - genetics

Autocrine Communication

Bone Morphogenetic Protein 7

Bone Morphogenetic Proteins - genetics

Bone Morphogenetic Proteins - metabolism

Bone Morphogenetic Proteins - secretion

Carrier Proteins - metabolism

Cell Culture Techniques

Cell Line, Tumor

Cell Movement

Cell Proliferation

Growth Inhibitors - metabolism

Humans

Melanocytes - metabolism

Melanoma - metabolism

Melanoma - pathology

Melanoma - secretion

Neoplasm Invasiveness

Transduction, Genetic

Transforming Growth Factor beta - genetics

Transforming Growth Factor beta - metabolism

Transforming Growth Factor beta - secretion

Up-Regulation

Details

Title: Subtitle: Aggressive melanoma cells escape from BMP7-mediated autocrine growth inhibition through coordinated Noggin upregulation
Creators: Mei-Yu Hsu - Brigham and Women's Hospital
Sherry A Rovinsky - Roy J. and Lucille A. Carver College of Medicine
Chiou-Yan Lai - Brigham and Women's Hospital
Shadi Qasem - Roy J. and Lucille A. Carver College of Medicine
Xiaoming Liu - Roy J. and Lucille A. Carver College of Medicine
Joan How - Brigham and Women's Hospital
John F Engelhardt - Roy J. and Lucille A. Carver College of Medicine
George F Murphy - Brigham and Women's Hospital
Resource Type: Journal article
Publication Details: Laboratory investigation, Vol.88(8), pp.842-855
DOI: 10.1038/labinvest.2008.55
PMID: 18560367
PMCID: PMC2676927
NLM abbreviation: Lab Invest
ISSN: 0023-6837
eISSN: 1530-0307
Grant note: P30 AR042689 / NIAMS NIH HHS R01 HL084815-17 / NHLBI NIH HHS DK047967 / NIDDK NIH HHS U19 AI029530-170009 / NIAID NIH HHS AR42689 / NIAMS NIH HHS P30 AR042689-159006 / NIAMS NIH HHS CA93683 / NCI NIH HHS HL084815 / NHLBI NIH HHS R01 DK047967 / NIDDK NIH HHS P50 CA093683 / NCI NIH HHS R01 HL084815 / NHLBI NIH HHS R01 DK047967-16 / NIDDK NIH HHS R37 DK047967 / NIDDK NIH HHS P50 CA093683-06A29006 / NCI NIH HHS P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 08/2008
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
Record Identifier: 9984284345002771

Metrics

24 Record Views

36 Times Cited - Web of Science