Metastatic breast cancer cells colonize and degrade three-dimensional osteoblastic tissue in vitro

Ravi Dhurjati, Venkatesh Krishnan, Laurie A. Shuman, Andrea Marie Mastro, Erwin A. Vogler

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Metastatic breast cancer cells (BCs) colonize a mineralized three-dimensional (3D) osteoblastic tissue (OT) grown from isolated pre-osteoblasts for up to 5 months in a specialized bioreactor. Sequential stages of BC interaction with OT include BC adhesion, penetration, colony formation, and OT reorganization into "Indian files" paralleling BC colonies, heretofore observed only in authentic pathological cancer tissue. BCs permeabilize OT by degrading the extra-cellular collagenous matrix (ECM) in which the osteoblasts are embedded. OT maturity (characterized by culture age and cell phenotype) profoundly affects the patterns of BC colonization. BCs rapidly form colonies on immature OT (higher cell/ECM ratio, osteoblastic phenotype) but fail to completely penetrate OT. By contrast, BCs efficiently penetrate mature OT (lower cell/ECM ratio, osteocytic phenotype) and reorganize OT. BC colonization provokes a strong osteoblast inflammatory response marked by increased expression of the pro-inflammatory cytokine IL-6. Furthermore, BCs inhibit osteoblastic bone formation by down-regulating synthesis of collagen and osteocalcin. Results strongly suggest that breast cancer disrupts the process of osteoblastic bone formation, in addition to upregulating osteoclastic bone resorption as widely reported. These observations may help explain why administration of bisphosphonates to humans with osteolytic metastases slows lesion progression by inhibiting osteoclasts but does not bring about osteoblast-mediated healing.

Original languageEnglish (US)
Pages (from-to)741-752
Number of pages12
JournalClinical and Experimental Metastasis
Volume25
Issue number7
DOIs
StatePublished - Nov 1 2008

Fingerprint

Breast Neoplasms
Osteoblasts
Phenotype
Osteogenesis
In Vitro Techniques
Osteocalcin
Diphosphonates
Bioreactors
Osteoclasts
Bone Resorption
Cell Adhesion
Cell Communication
Interleukin-6
Collagen
Cell Culture Techniques
Cytokines
Neoplasm Metastasis
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Dhurjati, Ravi ; Krishnan, Venkatesh ; Shuman, Laurie A. ; Mastro, Andrea Marie ; Vogler, Erwin A. / Metastatic breast cancer cells colonize and degrade three-dimensional osteoblastic tissue in vitro. In: Clinical and Experimental Metastasis. 2008 ; Vol. 25, No. 7. pp. 741-752.
@article{56e813f10cf047a88c10f0665c7dd289,
title = "Metastatic breast cancer cells colonize and degrade three-dimensional osteoblastic tissue in vitro",
abstract = "Metastatic breast cancer cells (BCs) colonize a mineralized three-dimensional (3D) osteoblastic tissue (OT) grown from isolated pre-osteoblasts for up to 5 months in a specialized bioreactor. Sequential stages of BC interaction with OT include BC adhesion, penetration, colony formation, and OT reorganization into {"}Indian files{"} paralleling BC colonies, heretofore observed only in authentic pathological cancer tissue. BCs permeabilize OT by degrading the extra-cellular collagenous matrix (ECM) in which the osteoblasts are embedded. OT maturity (characterized by culture age and cell phenotype) profoundly affects the patterns of BC colonization. BCs rapidly form colonies on immature OT (higher cell/ECM ratio, osteoblastic phenotype) but fail to completely penetrate OT. By contrast, BCs efficiently penetrate mature OT (lower cell/ECM ratio, osteocytic phenotype) and reorganize OT. BC colonization provokes a strong osteoblast inflammatory response marked by increased expression of the pro-inflammatory cytokine IL-6. Furthermore, BCs inhibit osteoblastic bone formation by down-regulating synthesis of collagen and osteocalcin. Results strongly suggest that breast cancer disrupts the process of osteoblastic bone formation, in addition to upregulating osteoclastic bone resorption as widely reported. These observations may help explain why administration of bisphosphonates to humans with osteolytic metastases slows lesion progression by inhibiting osteoclasts but does not bring about osteoblast-mediated healing.",
author = "Ravi Dhurjati and Venkatesh Krishnan and Shuman, {Laurie A.} and Mastro, {Andrea Marie} and Vogler, {Erwin A.}",
year = "2008",
month = "11",
day = "1",
doi = "10.1007/s10585-008-9185-z",
language = "English (US)",
volume = "25",
pages = "741--752",
journal = "Clinical and Experimental Metastasis",
issn = "0262-0898",
publisher = "Springer Netherlands",
number = "7",

}

Metastatic breast cancer cells colonize and degrade three-dimensional osteoblastic tissue in vitro. / Dhurjati, Ravi; Krishnan, Venkatesh; Shuman, Laurie A.; Mastro, Andrea Marie; Vogler, Erwin A.

In: Clinical and Experimental Metastasis, Vol. 25, No. 7, 01.11.2008, p. 741-752.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Metastatic breast cancer cells colonize and degrade three-dimensional osteoblastic tissue in vitro

AU - Dhurjati, Ravi

AU - Krishnan, Venkatesh

AU - Shuman, Laurie A.

AU - Mastro, Andrea Marie

AU - Vogler, Erwin A.

PY - 2008/11/1

Y1 - 2008/11/1

N2 - Metastatic breast cancer cells (BCs) colonize a mineralized three-dimensional (3D) osteoblastic tissue (OT) grown from isolated pre-osteoblasts for up to 5 months in a specialized bioreactor. Sequential stages of BC interaction with OT include BC adhesion, penetration, colony formation, and OT reorganization into "Indian files" paralleling BC colonies, heretofore observed only in authentic pathological cancer tissue. BCs permeabilize OT by degrading the extra-cellular collagenous matrix (ECM) in which the osteoblasts are embedded. OT maturity (characterized by culture age and cell phenotype) profoundly affects the patterns of BC colonization. BCs rapidly form colonies on immature OT (higher cell/ECM ratio, osteoblastic phenotype) but fail to completely penetrate OT. By contrast, BCs efficiently penetrate mature OT (lower cell/ECM ratio, osteocytic phenotype) and reorganize OT. BC colonization provokes a strong osteoblast inflammatory response marked by increased expression of the pro-inflammatory cytokine IL-6. Furthermore, BCs inhibit osteoblastic bone formation by down-regulating synthesis of collagen and osteocalcin. Results strongly suggest that breast cancer disrupts the process of osteoblastic bone formation, in addition to upregulating osteoclastic bone resorption as widely reported. These observations may help explain why administration of bisphosphonates to humans with osteolytic metastases slows lesion progression by inhibiting osteoclasts but does not bring about osteoblast-mediated healing.

AB - Metastatic breast cancer cells (BCs) colonize a mineralized three-dimensional (3D) osteoblastic tissue (OT) grown from isolated pre-osteoblasts for up to 5 months in a specialized bioreactor. Sequential stages of BC interaction with OT include BC adhesion, penetration, colony formation, and OT reorganization into "Indian files" paralleling BC colonies, heretofore observed only in authentic pathological cancer tissue. BCs permeabilize OT by degrading the extra-cellular collagenous matrix (ECM) in which the osteoblasts are embedded. OT maturity (characterized by culture age and cell phenotype) profoundly affects the patterns of BC colonization. BCs rapidly form colonies on immature OT (higher cell/ECM ratio, osteoblastic phenotype) but fail to completely penetrate OT. By contrast, BCs efficiently penetrate mature OT (lower cell/ECM ratio, osteocytic phenotype) and reorganize OT. BC colonization provokes a strong osteoblast inflammatory response marked by increased expression of the pro-inflammatory cytokine IL-6. Furthermore, BCs inhibit osteoblastic bone formation by down-regulating synthesis of collagen and osteocalcin. Results strongly suggest that breast cancer disrupts the process of osteoblastic bone formation, in addition to upregulating osteoclastic bone resorption as widely reported. These observations may help explain why administration of bisphosphonates to humans with osteolytic metastases slows lesion progression by inhibiting osteoclasts but does not bring about osteoblast-mediated healing.

UR - http://www.scopus.com/inward/record.url?scp=53949085763&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53949085763&partnerID=8YFLogxK

U2 - 10.1007/s10585-008-9185-z

DO - 10.1007/s10585-008-9185-z

M3 - Article

C2 - 18543066

AN - SCOPUS:53949085763

VL - 25

SP - 741

EP - 752

JO - Clinical and Experimental Metastasis

JF - Clinical and Experimental Metastasis

SN - 0262-0898

IS - 7

ER -