RANKL/RANK/MMP-1 Molecular Triad Contributes to the Metastatic Phenotype of Breast and Prostate Cancer Cells In Vitro

Sandra Casimiro, Khalid Mohammad, Ricardo Pires, Joana Tato-Costa, Irina Alho, Rui Teixeira, António Carvalho, Sofia Ribeiro, Allan Lipton, Theresa Guise, Luis Costa

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The osteolytic nature of bone metastasis results from a tumor-driven increased bone resorption. Bone remodeling is orchestrated by the molecular triad RANK-RANKL-OPG. This process is dysregulated in bone metastases, mostly via induction of RANKL by tumor-derived factors. These factors increase expression of RANKL, which induce osteoclast formation, function, and survival, thereby increasing bone resorption. RANK is unexpectedly expressed by cancer cells, and the activation of RANKL-RANK pathway correlates with an increased invasive phenotype. To investigate the interaction between RANK expression in human breast and prostate cancer cells and their pro-metastatic phenotype we analyzed the activation of RANKL-RANK pathway and its effects on cell migration, invasion, gene expression in vitro, and osteolysis-inducing ability in vivo. RANKL activates kinase signaling pathways, stimulates cell migration, increases cell invasion, and up-regulates MMP-1 expression. In vivo, MMP-1 knockdown resulted in smaller x-ray osteolytic lesions and osteoclastogenesis, and decreased tumor burden. Therefore, RANKL inhibition in bone metastatic disease may decrease the levels of the osteoclastogenesis inducer MMP-1, contributing to a better clinical outcome.

Original languageEnglish
Article numbere63153
JournalPLoS One
Volume8
Issue number5
DOIs
StatePublished - May 16 2013

Fingerprint

interstitial collagenase
prostatic neoplasms
Matrix Metalloproteinases
breast neoplasms
Prostatic Neoplasms
Bone
bone resorption
Cells
bones
Bone Resorption
Breast Neoplasms
Phenotype
cell movement
phenotype
Osteogenesis
metastasis
neoplasms
Cell Movement
Neoplasm Metastasis
bone diseases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

RANKL/RANK/MMP-1 Molecular Triad Contributes to the Metastatic Phenotype of Breast and Prostate Cancer Cells In Vitro. / Casimiro, Sandra; Mohammad, Khalid; Pires, Ricardo; Tato-Costa, Joana; Alho, Irina; Teixeira, Rui; Carvalho, António; Ribeiro, Sofia; Lipton, Allan; Guise, Theresa; Costa, Luis.

In: PLoS One, Vol. 8, No. 5, e63153, 16.05.2013.

Research output: Contribution to journalArticle

Casimiro, S, Mohammad, K, Pires, R, Tato-Costa, J, Alho, I, Teixeira, R, Carvalho, A, Ribeiro, S, Lipton, A, Guise, T & Costa, L 2013, 'RANKL/RANK/MMP-1 Molecular Triad Contributes to the Metastatic Phenotype of Breast and Prostate Cancer Cells In Vitro', PLoS One, vol. 8, no. 5, e63153. https://doi.org/10.1371/journal.pone.0063153
Casimiro, Sandra ; Mohammad, Khalid ; Pires, Ricardo ; Tato-Costa, Joana ; Alho, Irina ; Teixeira, Rui ; Carvalho, António ; Ribeiro, Sofia ; Lipton, Allan ; Guise, Theresa ; Costa, Luis. / RANKL/RANK/MMP-1 Molecular Triad Contributes to the Metastatic Phenotype of Breast and Prostate Cancer Cells In Vitro. In: PLoS One. 2013 ; Vol. 8, No. 5.
@article{5f258ce2c5cf4b0f8668c083df0e7a4b,
title = "RANKL/RANK/MMP-1 Molecular Triad Contributes to the Metastatic Phenotype of Breast and Prostate Cancer Cells In Vitro",
abstract = "The osteolytic nature of bone metastasis results from a tumor-driven increased bone resorption. Bone remodeling is orchestrated by the molecular triad RANK-RANKL-OPG. This process is dysregulated in bone metastases, mostly via induction of RANKL by tumor-derived factors. These factors increase expression of RANKL, which induce osteoclast formation, function, and survival, thereby increasing bone resorption. RANK is unexpectedly expressed by cancer cells, and the activation of RANKL-RANK pathway correlates with an increased invasive phenotype. To investigate the interaction between RANK expression in human breast and prostate cancer cells and their pro-metastatic phenotype we analyzed the activation of RANKL-RANK pathway and its effects on cell migration, invasion, gene expression in vitro, and osteolysis-inducing ability in vivo. RANKL activates kinase signaling pathways, stimulates cell migration, increases cell invasion, and up-regulates MMP-1 expression. In vivo, MMP-1 knockdown resulted in smaller x-ray osteolytic lesions and osteoclastogenesis, and decreased tumor burden. Therefore, RANKL inhibition in bone metastatic disease may decrease the levels of the osteoclastogenesis inducer MMP-1, contributing to a better clinical outcome.",
author = "Sandra Casimiro and Khalid Mohammad and Ricardo Pires and Joana Tato-Costa and Irina Alho and Rui Teixeira and Ant{\'o}nio Carvalho and Sofia Ribeiro and Allan Lipton and Theresa Guise and Luis Costa",
year = "2013",
month = "5",
day = "16",
doi = "10.1371/journal.pone.0063153",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - RANKL/RANK/MMP-1 Molecular Triad Contributes to the Metastatic Phenotype of Breast and Prostate Cancer Cells In Vitro

AU - Casimiro, Sandra

AU - Mohammad, Khalid

AU - Pires, Ricardo

AU - Tato-Costa, Joana

AU - Alho, Irina

AU - Teixeira, Rui

AU - Carvalho, António

AU - Ribeiro, Sofia

AU - Lipton, Allan

AU - Guise, Theresa

AU - Costa, Luis

PY - 2013/5/16

Y1 - 2013/5/16

N2 - The osteolytic nature of bone metastasis results from a tumor-driven increased bone resorption. Bone remodeling is orchestrated by the molecular triad RANK-RANKL-OPG. This process is dysregulated in bone metastases, mostly via induction of RANKL by tumor-derived factors. These factors increase expression of RANKL, which induce osteoclast formation, function, and survival, thereby increasing bone resorption. RANK is unexpectedly expressed by cancer cells, and the activation of RANKL-RANK pathway correlates with an increased invasive phenotype. To investigate the interaction between RANK expression in human breast and prostate cancer cells and their pro-metastatic phenotype we analyzed the activation of RANKL-RANK pathway and its effects on cell migration, invasion, gene expression in vitro, and osteolysis-inducing ability in vivo. RANKL activates kinase signaling pathways, stimulates cell migration, increases cell invasion, and up-regulates MMP-1 expression. In vivo, MMP-1 knockdown resulted in smaller x-ray osteolytic lesions and osteoclastogenesis, and decreased tumor burden. Therefore, RANKL inhibition in bone metastatic disease may decrease the levels of the osteoclastogenesis inducer MMP-1, contributing to a better clinical outcome.

AB - The osteolytic nature of bone metastasis results from a tumor-driven increased bone resorption. Bone remodeling is orchestrated by the molecular triad RANK-RANKL-OPG. This process is dysregulated in bone metastases, mostly via induction of RANKL by tumor-derived factors. These factors increase expression of RANKL, which induce osteoclast formation, function, and survival, thereby increasing bone resorption. RANK is unexpectedly expressed by cancer cells, and the activation of RANKL-RANK pathway correlates with an increased invasive phenotype. To investigate the interaction between RANK expression in human breast and prostate cancer cells and their pro-metastatic phenotype we analyzed the activation of RANKL-RANK pathway and its effects on cell migration, invasion, gene expression in vitro, and osteolysis-inducing ability in vivo. RANKL activates kinase signaling pathways, stimulates cell migration, increases cell invasion, and up-regulates MMP-1 expression. In vivo, MMP-1 knockdown resulted in smaller x-ray osteolytic lesions and osteoclastogenesis, and decreased tumor burden. Therefore, RANKL inhibition in bone metastatic disease may decrease the levels of the osteoclastogenesis inducer MMP-1, contributing to a better clinical outcome.

UR - http://www.scopus.com/inward/record.url?scp=84877807530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877807530&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0063153

DO - 10.1371/journal.pone.0063153

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e63153

ER -