NDLI: Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells

Content Provider	PubMed Central
Author	Ruppender, Nazanin S. Merkel, Alyssa R. Martin, T. John Mundy, Gregory R. Sterling, Julie A. Guelcher, Scott A.
Editor	Aziz, Syed A.
Abstract	Nearly 70% of breast cancer patients with advanced disease will develop bone metastases. Once established in bone, tumor cells produce factors that cause changes in normal bone remodeling, such as parathyroid hormone-related protein (PTHrP). While enhanced expression of PTHrP is known to stimulate osteoclasts to resorb bone, the environmental factors driving tumor cells to express PTHrP in the early stages of development of metastatic bone disease are unknown. In this study, we have shown that tumor cells known to metastasize to bone respond to 2D substrates with rigidities comparable to that of the bone microenvironment by increasing expression and production of PTHrP. The cellular response is regulated by Rho-dependent actomyosin contractility mediated by TGF-ß signaling. Inhibition of Rho-associated kinase (ROCK) using both pharmacological and genetic approaches decreased PTHrP expression. Furthermore, cells expressing a dominant negative form of the TGF-ß receptor did not respond to substrate rigidity, and inhibition of ROCK decreased PTHrP expression induced by exogenous TGF-ß. These observations suggest a role for the differential rigidity of the mineralized bone microenvironment in early stages of tumor-induced osteolysis, which is especially important in metastatic cancer since many cancers (such as those of the breast and lung) preferentially metastasize to bone.
Related Links	http://dx.doi.org/10.1371/journal.pone.0015451
Starting Page	15451
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	11
Volume Number	5
Language	English
Publisher	Public Library of Science
Publisher Date	2010-11-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells

Functional Analysis of Prognostic Gene Expression Network Genes in Metastatic Breast Cancer Models

Heterogeneity of Estrogen Receptor Expression in Circulating Tumor Cells from Metastatic Breast Cancer Patients

Expression of Lipid Metabolism-Related Proteins in Metastatic Breast Cancer

Differential Matrix Rigidity Response in Breast Cancer Cell Lines Correlates with the Tissue Tropism

Effects of Different Tissue Microenvironments on Gene Expression in Breast Cancer Cells

Neoplastic and Stromal Cells Contribute to an Extracellular Matrix Gene Expression Profile Defining a Breast Cancer Subtype Likely to Progress

Enhanced Invasion of Metastatic Cancer Cells via Extracellular Matrix Interface

Breast Cancer Cells Induce Osteolytic Bone Lesions In vivo through a Reduction in Osteoblast Activity in Mice

Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells

Similar Documents

Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells

Functional Analysis of Prognostic Gene Expression Network Genes in Metastatic Breast Cancer Models

Heterogeneity of Estrogen Receptor Expression in Circulating Tumor Cells from Metastatic Breast Cancer Patients

Expression of Lipid Metabolism-Related Proteins in Metastatic Breast Cancer

Differential Matrix Rigidity Response in Breast Cancer Cell Lines Correlates with the Tissue Tropism

Effects of Different Tissue Microenvironments on Gene Expression in Breast Cancer Cells

Neoplastic and Stromal Cells Contribute to an Extracellular Matrix Gene Expression Profile Defining a Breast Cancer Subtype Likely to Progress

Enhanced Invasion of Metastatic Cancer Cells via Extracellular Matrix Interface

Breast Cancer Cells Induce Osteolytic Bone Lesions In vivo through a Reduction in Osteoblast Activity in Mice

Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells