Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation
<p>Abstract</p> <p>Background</p> <p>The tumor microenvironment is pivotal in tumor progression. Thus, we aimed to develop a mammary tumor model to elucidate molecular characteristics in the stroma versus the tumor cell compartment by global gene expression. Secondly, s...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-01-01
|
| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/12/21 |
| _version_ | 1818640426969595904 |
|---|---|
| author | Moen Ingrid Jevne Charlotte Wang Jian Kalland Karl-Henning Chekenya Martha Akslen Lars A Sleire Linda Enger Per Ø Reed Rolf K Øyan Anne M Stuhr Linda EB |
| author_facet | Moen Ingrid Jevne Charlotte Wang Jian Kalland Karl-Henning Chekenya Martha Akslen Lars A Sleire Linda Enger Per Ø Reed Rolf K Øyan Anne M Stuhr Linda EB |
| author_sort | Moen Ingrid |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The tumor microenvironment is pivotal in tumor progression. Thus, we aimed to develop a mammary tumor model to elucidate molecular characteristics in the stroma versus the tumor cell compartment by global gene expression. Secondly, since tumor hypoxia influences several aspects of tumor pathophysiology, we hypothesized that hyperoxia might have an inhibitory effect on tumor growth <it>per se</it>. Finally, we aimed to identify differences in gene expression and key molecular mechanisms, both in the native state and following treatment.</p> <p>Methods</p> <p>4T1 dsRed breast cancer cells were injected into eGFP expressing NOD/SCID mice. Group 1 was exposed to 3 intermittent HBO treatments (Day 1, 4 and 7), Group 2 to 7 daily HBO treatments (both 2.5bar, 100% O<sub>2</sub>, à 90 min), whereas the controls were exposed to a normal atmosphere. Tumor growth, histology, vascularisation, cell proliferation, cell death and metastasis were assessed. Fluorescence-activated cell sorting was used to separate tumor cells from stromal cells prior to gene expression analysis.</p> <p>Results</p> <p>The purity of sorted cells was verified by fluorescence microscopy. Gene expression profiling demonstrated that highly expressed genes in the untreated tumor stroma included constituents of the extracellular matrix and matrix metalloproteinases. Tumor growth was significantly inhibited by HBO, and the MAPK pathway was found to be significantly reduced. Immunohistochemistry indicated a significantly reduced microvessel density after intermittent HBO, whereas daily HBO did not show a similar effect. The anti-angiogenic response was reflected in the expression trends of angiogenic factors.</p> <p>Conclusions</p> <p>The present <it>in vivo </it>mammary tumor model enabled us to separate tumor and stromal cells, and demonstrated that the two compartments are characterized by distinct gene expressions, both in the native state and following HBO treatments. Furthermore, hyperoxia induced a significant tumor growth-inhibitory effect, with significant down-regulation of the MAPK pathway. An anti-angiogenic effect after intermittent HBO was observed, and reflected in the gene expression profile.</p> |
| first_indexed | 2024-12-16T23:11:05Z |
| format | Article |
| id | doaj.art-7f7fc43091ff4827ac115ce956238e4f |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-16T23:11:05Z |
| publishDate | 2012-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-7f7fc43091ff4827ac115ce956238e4f2022-12-21T22:12:25ZengBMCBMC Cancer1471-24072012-01-011212110.1186/1471-2407-12-21Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenationMoen IngridJevne CharlotteWang JianKalland Karl-HenningChekenya MarthaAkslen Lars ASleire LindaEnger Per ØReed Rolf KØyan Anne MStuhr Linda EB<p>Abstract</p> <p>Background</p> <p>The tumor microenvironment is pivotal in tumor progression. Thus, we aimed to develop a mammary tumor model to elucidate molecular characteristics in the stroma versus the tumor cell compartment by global gene expression. Secondly, since tumor hypoxia influences several aspects of tumor pathophysiology, we hypothesized that hyperoxia might have an inhibitory effect on tumor growth <it>per se</it>. Finally, we aimed to identify differences in gene expression and key molecular mechanisms, both in the native state and following treatment.</p> <p>Methods</p> <p>4T1 dsRed breast cancer cells were injected into eGFP expressing NOD/SCID mice. Group 1 was exposed to 3 intermittent HBO treatments (Day 1, 4 and 7), Group 2 to 7 daily HBO treatments (both 2.5bar, 100% O<sub>2</sub>, à 90 min), whereas the controls were exposed to a normal atmosphere. Tumor growth, histology, vascularisation, cell proliferation, cell death and metastasis were assessed. Fluorescence-activated cell sorting was used to separate tumor cells from stromal cells prior to gene expression analysis.</p> <p>Results</p> <p>The purity of sorted cells was verified by fluorescence microscopy. Gene expression profiling demonstrated that highly expressed genes in the untreated tumor stroma included constituents of the extracellular matrix and matrix metalloproteinases. Tumor growth was significantly inhibited by HBO, and the MAPK pathway was found to be significantly reduced. Immunohistochemistry indicated a significantly reduced microvessel density after intermittent HBO, whereas daily HBO did not show a similar effect. The anti-angiogenic response was reflected in the expression trends of angiogenic factors.</p> <p>Conclusions</p> <p>The present <it>in vivo </it>mammary tumor model enabled us to separate tumor and stromal cells, and demonstrated that the two compartments are characterized by distinct gene expressions, both in the native state and following HBO treatments. Furthermore, hyperoxia induced a significant tumor growth-inhibitory effect, with significant down-regulation of the MAPK pathway. An anti-angiogenic effect after intermittent HBO was observed, and reflected in the gene expression profile.</p>http://www.biomedcentral.com/1471-2407/12/21 |
| spellingShingle | Moen Ingrid Jevne Charlotte Wang Jian Kalland Karl-Henning Chekenya Martha Akslen Lars A Sleire Linda Enger Per Ø Reed Rolf K Øyan Anne M Stuhr Linda EB Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation BMC Cancer |
| title | Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation |
| title_full | Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation |
| title_fullStr | Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation |
| title_full_unstemmed | Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation |
| title_short | Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation |
| title_sort | gene expression in tumor cells and stroma in dsred 4t1 tumors in egfp expressing mice with and without enhanced oxygenation |
| url | http://www.biomedcentral.com/1471-2407/12/21 |
| work_keys_str_mv | AT moeningrid geneexpressionintumorcellsandstromaindsred4t1tumorsinegfpexpressingmicewithandwithoutenhancedoxygenation AT jevnecharlotte geneexpressionintumorcellsandstromaindsred4t1tumorsinegfpexpressingmicewithandwithoutenhancedoxygenation AT wangjian geneexpressionintumorcellsandstromaindsred4t1tumorsinegfpexpressingmicewithandwithoutenhancedoxygenation AT kallandkarlhenning geneexpressionintumorcellsandstromaindsred4t1tumorsinegfpexpressingmicewithandwithoutenhancedoxygenation AT chekenyamartha geneexpressionintumorcellsandstromaindsred4t1tumorsinegfpexpressingmicewithandwithoutenhancedoxygenation AT akslenlarsa geneexpressionintumorcellsandstromaindsred4t1tumorsinegfpexpressingmicewithandwithoutenhancedoxygenation AT sleirelinda geneexpressionintumorcellsandstromaindsred4t1tumorsinegfpexpressingmicewithandwithoutenhancedoxygenation AT engerperø geneexpressionintumorcellsandstromaindsred4t1tumorsinegfpexpressingmicewithandwithoutenhancedoxygenation AT reedrolfk geneexpressionintumorcellsandstromaindsred4t1tumorsinegfpexpressingmicewithandwithoutenhancedoxygenation AT øyanannem geneexpressionintumorcellsandstromaindsred4t1tumorsinegfpexpressingmicewithandwithoutenhancedoxygenation AT stuhrlindaeb geneexpressionintumorcellsandstromaindsred4t1tumorsinegfpexpressingmicewithandwithoutenhancedoxygenation |