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Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model
BACKGROUND: The bone-tumor microenvironment encompasses unique interactions between the normal cells of the bone and marrow cavity and the malignant cells from a primary or metastasized cancer. A multitude of paracrine factors within this microenvironment such as the growth factor, TGF-β, and the ch...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2644314/ https://www.ncbi.nlm.nih.gov/pubmed/19192289 http://dx.doi.org/10.1186/1471-2407-9-45 |
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author | Schiller, Katherine R Zillhardt, Marion R Alley, Jeremy Borjesson, Dori L Beitz, Alvin J Mauro, Laura J |
author_facet | Schiller, Katherine R Zillhardt, Marion R Alley, Jeremy Borjesson, Dori L Beitz, Alvin J Mauro, Laura J |
author_sort | Schiller, Katherine R |
collection | PubMed |
description | BACKGROUND: The bone-tumor microenvironment encompasses unique interactions between the normal cells of the bone and marrow cavity and the malignant cells from a primary or metastasized cancer. A multitude of paracrine factors within this microenvironment such as the growth factor, TGF-β, and the chemokine, MCP-1, are secreted by many of these cell types. These factors can act in concert to modulate normal and malignant cell proliferation, malignant cell migration and invasion and, often, mediate bone cancer pain. Although many valuable in vitro and in vivo models exist, identifying the relevant paracrine factors and deciphering their interactions is still a challenge. The aim of our study is to test an ex vivo coculture model that will allow monitoring of the expression, release and regulation of paracrine factors during interactions of an intact femur explant and tumor cells. METHODS: Intact or marrow-depleted neonatal mouse femurs and select murine and human sarcoma or carcinoma cell lines were incubated singly or in coculture in specialized well plates. Viability of the bone and cells was determined by immunohistochemical stains, microscopy and marrow cytopreps. Secretion and mRNA expression of paracrine factors was quantitated by ELISA and real-time RT-PCR. RESULTS: Compartments of the bone were optimally viable for up to 48 h in culture and tumor cells for up to 4 days. Bone was the major contributor of TGF-β and MMP2 whereas both bone and sarcoma cells secreted the chemokine MCP-1 in cocultures. Synergistic interaction between the femur and sarcoma resulted in enhanced MCP-1 secretion and expression in cocultures and was dependent on the presence of the hematopoietic component of the bone as well as other bone cells. In contrast, coculturing with breast carcinoma cells resulted in reduction of TGF-β and MCP-1 secretion from the bone. CONCLUSION: These studies illustrate the feasibility of this model to examine paracrine interactions between intact bone and tumor cells. Further study of unique regulation of MCP-1 secretion and signaling between these cell types in different types of cancer will be possible using this simulated microenvironment. |
format | Text |
id | pubmed-2644314 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-26443142009-02-18 Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model Schiller, Katherine R Zillhardt, Marion R Alley, Jeremy Borjesson, Dori L Beitz, Alvin J Mauro, Laura J BMC Cancer Research Article BACKGROUND: The bone-tumor microenvironment encompasses unique interactions between the normal cells of the bone and marrow cavity and the malignant cells from a primary or metastasized cancer. A multitude of paracrine factors within this microenvironment such as the growth factor, TGF-β, and the chemokine, MCP-1, are secreted by many of these cell types. These factors can act in concert to modulate normal and malignant cell proliferation, malignant cell migration and invasion and, often, mediate bone cancer pain. Although many valuable in vitro and in vivo models exist, identifying the relevant paracrine factors and deciphering their interactions is still a challenge. The aim of our study is to test an ex vivo coculture model that will allow monitoring of the expression, release and regulation of paracrine factors during interactions of an intact femur explant and tumor cells. METHODS: Intact or marrow-depleted neonatal mouse femurs and select murine and human sarcoma or carcinoma cell lines were incubated singly or in coculture in specialized well plates. Viability of the bone and cells was determined by immunohistochemical stains, microscopy and marrow cytopreps. Secretion and mRNA expression of paracrine factors was quantitated by ELISA and real-time RT-PCR. RESULTS: Compartments of the bone were optimally viable for up to 48 h in culture and tumor cells for up to 4 days. Bone was the major contributor of TGF-β and MMP2 whereas both bone and sarcoma cells secreted the chemokine MCP-1 in cocultures. Synergistic interaction between the femur and sarcoma resulted in enhanced MCP-1 secretion and expression in cocultures and was dependent on the presence of the hematopoietic component of the bone as well as other bone cells. In contrast, coculturing with breast carcinoma cells resulted in reduction of TGF-β and MCP-1 secretion from the bone. CONCLUSION: These studies illustrate the feasibility of this model to examine paracrine interactions between intact bone and tumor cells. Further study of unique regulation of MCP-1 secretion and signaling between these cell types in different types of cancer will be possible using this simulated microenvironment. BioMed Central 2009-02-03 /pmc/articles/PMC2644314/ /pubmed/19192289 http://dx.doi.org/10.1186/1471-2407-9-45 Text en Copyright ©2009 Schiller et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Schiller, Katherine R Zillhardt, Marion R Alley, Jeremy Borjesson, Dori L Beitz, Alvin J Mauro, Laura J Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model |
title | Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model |
title_full | Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model |
title_fullStr | Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model |
title_full_unstemmed | Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model |
title_short | Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model |
title_sort | secretion of mcp-1 and other paracrine factors in a novel tumor-bone coculture model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2644314/ https://www.ncbi.nlm.nih.gov/pubmed/19192289 http://dx.doi.org/10.1186/1471-2407-9-45 |
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