Mathematical modelling of the influence of heat shock proteins on cancer invasion of tissue
Tumour cell invasion is crucial for cancer metastasis, which is the main cause of cancer mortality. An important group of proteins involved in cancer invasion are the Heat Shock Proteins (HSPs). According to experimental data, inhibition of one of these proteins, Hsp90, slows down cancer cells while...
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Veröffentlicht in: | Journal of mathematical biology 2009-04, Vol.58 (4-5), p.819-844 |
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description | Tumour cell invasion is crucial for cancer metastasis, which is the main cause of cancer mortality. An important group of proteins involved in cancer invasion are the Heat Shock Proteins (HSPs). According to experimental data, inhibition of one of these proteins, Hsp90, slows down cancer cells while they are invading tissue, but does not affect the synthesis of matrix metalloproteinases (MMP2 and MMP9), which are very important for cancer metastasis, acting as extracellular matrix (ECM) degrading enzymes. To test different biological hypotheses regarding how precisely Hsp90 influences tumour invasion, in this paper we use a model of solid tumour growth which accounts for the interactions between Hsp90 dynamics and the migration of cancer cells and, alternatively, between Hsp90 dynamics and the synthesis of matrix degrading enzymes (MDEs). The model consists of a system of reaction-diffusion-taxis partial differential equations describing interactions between cancer cells, MDE, and the host tissue (ECM). Using numerical simulations we investigate the effects of the administration of Hsp90 inhibitors on the dynamics of tumour invasion. Alternative mechanisms of reduction of cancer invasiveness result in different simulated patterns of the invading tumour cells. Therefore, predictions of the model suggest experiments which might be performed to develop a deeper understanding of the tumour invasion process. |
doi_str_mv | 10.1007/s00285-008-0220-0 |
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An important group of proteins involved in cancer invasion are the Heat Shock Proteins (HSPs). According to experimental data, inhibition of one of these proteins, Hsp90, slows down cancer cells while they are invading tissue, but does not affect the synthesis of matrix metalloproteinases (MMP2 and MMP9), which are very important for cancer metastasis, acting as extracellular matrix (ECM) degrading enzymes. To test different biological hypotheses regarding how precisely Hsp90 influences tumour invasion, in this paper we use a model of solid tumour growth which accounts for the interactions between Hsp90 dynamics and the migration of cancer cells and, alternatively, between Hsp90 dynamics and the synthesis of matrix degrading enzymes (MDEs). The model consists of a system of reaction-diffusion-taxis partial differential equations describing interactions between cancer cells, MDE, and the host tissue (ECM). Using numerical simulations we investigate the effects of the administration of Hsp90 inhibitors on the dynamics of tumour invasion. Alternative mechanisms of reduction of cancer invasiveness result in different simulated patterns of the invading tumour cells. Therefore, predictions of the model suggest experiments which might be performed to develop a deeper understanding of the tumour invasion process.</description><identifier>ISSN: 0303-6812</identifier><identifier>EISSN: 1432-1416</identifier><identifier>DOI: 10.1007/s00285-008-0220-0</identifier><identifier>PMID: 18807037</identifier><language>eng</language><publisher>Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag</publisher><subject>Animals ; Applications of Mathematics ; Biomechanical Phenomena ; Breast Neoplasms - pathology ; Breast Neoplasms - physiopathology ; Cancer invasion ; Cell Count ; Cell Line, Tumor ; Computer Simulation ; Extracellular Matrix - physiology ; Female ; Haptotaxis ; heat shock proteins ; Heat-Shock Proteins - physiology ; HSP90 Heat-Shock Proteins - physiology ; Humans ; Mathematical and Computational Biology ; Mathematical Concepts ; Mathematics ; Mathematics and Statistics ; Matrix Metalloproteinases - physiology ; Models, Biological ; Neoplasm Invasiveness - pathology ; Neoplasm Invasiveness - physiopathology ; Neoplasm Proteins - physiology</subject><ispartof>Journal of mathematical biology, 2009-04, Vol.58 (4-5), p.819-844</ispartof><rights>Springer-Verlag 2008</rights><rights>Springer-Verlag 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-6566135f3695983a93eec77e41a6c2b2560e1b114bc9db54759394dc1f72d9da3</citedby><cites>FETCH-LOGICAL-c393t-6566135f3695983a93eec77e41a6c2b2560e1b114bc9db54759394dc1f72d9da3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00285-008-0220-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00285-008-0220-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18807037$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Szymaska, Zuzanna</creatorcontrib><creatorcontrib>Urbaski, Jakub</creatorcontrib><creatorcontrib>Marciniak-czochra, Anna</creatorcontrib><title>Mathematical modelling of the influence of heat shock proteins on cancer invasion of tissue</title><title>Journal of mathematical biology</title><addtitle>J. Math. Biol</addtitle><addtitle>J Math Biol</addtitle><description>Tumour cell invasion is crucial for cancer metastasis, which is the main cause of cancer mortality. An important group of proteins involved in cancer invasion are the Heat Shock Proteins (HSPs). According to experimental data, inhibition of one of these proteins, Hsp90, slows down cancer cells while they are invading tissue, but does not affect the synthesis of matrix metalloproteinases (MMP2 and MMP9), which are very important for cancer metastasis, acting as extracellular matrix (ECM) degrading enzymes. To test different biological hypotheses regarding how precisely Hsp90 influences tumour invasion, in this paper we use a model of solid tumour growth which accounts for the interactions between Hsp90 dynamics and the migration of cancer cells and, alternatively, between Hsp90 dynamics and the synthesis of matrix degrading enzymes (MDEs). The model consists of a system of reaction-diffusion-taxis partial differential equations describing interactions between cancer cells, MDE, and the host tissue (ECM). Using numerical simulations we investigate the effects of the administration of Hsp90 inhibitors on the dynamics of tumour invasion. Alternative mechanisms of reduction of cancer invasiveness result in different simulated patterns of the invading tumour cells. Therefore, predictions of the model suggest experiments which might be performed to develop a deeper understanding of the tumour invasion process.</description><subject>Animals</subject><subject>Applications of Mathematics</subject><subject>Biomechanical Phenomena</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - physiopathology</subject><subject>Cancer invasion</subject><subject>Cell Count</subject><subject>Cell Line, Tumor</subject><subject>Computer Simulation</subject><subject>Extracellular Matrix - physiology</subject><subject>Female</subject><subject>Haptotaxis</subject><subject>heat shock proteins</subject><subject>Heat-Shock Proteins - physiology</subject><subject>HSP90 Heat-Shock Proteins - physiology</subject><subject>Humans</subject><subject>Mathematical and Computational Biology</subject><subject>Mathematical Concepts</subject><subject>Mathematics</subject><subject>Mathematics and Statistics</subject><subject>Matrix Metalloproteinases - physiology</subject><subject>Models, Biological</subject><subject>Neoplasm Invasiveness - 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Academic</collection><jtitle>Journal of mathematical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Szymaska, Zuzanna</au><au>Urbaski, Jakub</au><au>Marciniak-czochra, Anna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mathematical modelling of the influence of heat shock proteins on cancer invasion of tissue</atitle><jtitle>Journal of mathematical biology</jtitle><stitle>J. Math. Biol</stitle><addtitle>J Math Biol</addtitle><date>2009-04-01</date><risdate>2009</risdate><volume>58</volume><issue>4-5</issue><spage>819</spage><epage>844</epage><pages>819-844</pages><issn>0303-6812</issn><eissn>1432-1416</eissn><abstract>Tumour cell invasion is crucial for cancer metastasis, which is the main cause of cancer mortality. An important group of proteins involved in cancer invasion are the Heat Shock Proteins (HSPs). According to experimental data, inhibition of one of these proteins, Hsp90, slows down cancer cells while they are invading tissue, but does not affect the synthesis of matrix metalloproteinases (MMP2 and MMP9), which are very important for cancer metastasis, acting as extracellular matrix (ECM) degrading enzymes. To test different biological hypotheses regarding how precisely Hsp90 influences tumour invasion, in this paper we use a model of solid tumour growth which accounts for the interactions between Hsp90 dynamics and the migration of cancer cells and, alternatively, between Hsp90 dynamics and the synthesis of matrix degrading enzymes (MDEs). The model consists of a system of reaction-diffusion-taxis partial differential equations describing interactions between cancer cells, MDE, and the host tissue (ECM). Using numerical simulations we investigate the effects of the administration of Hsp90 inhibitors on the dynamics of tumour invasion. Alternative mechanisms of reduction of cancer invasiveness result in different simulated patterns of the invading tumour cells. Therefore, predictions of the model suggest experiments which might be performed to develop a deeper understanding of the tumour invasion process.</abstract><cop>Berlin/Heidelberg</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>18807037</pmid><doi>10.1007/s00285-008-0220-0</doi><tpages>26</tpages></addata></record> |
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subjects | Animals Applications of Mathematics Biomechanical Phenomena Breast Neoplasms - pathology Breast Neoplasms - physiopathology Cancer invasion Cell Count Cell Line, Tumor Computer Simulation Extracellular Matrix - physiology Female Haptotaxis heat shock proteins Heat-Shock Proteins - physiology HSP90 Heat-Shock Proteins - physiology Humans Mathematical and Computational Biology Mathematical Concepts Mathematics Mathematics and Statistics Matrix Metalloproteinases - physiology Models, Biological Neoplasm Invasiveness - pathology Neoplasm Invasiveness - physiopathology Neoplasm Proteins - physiology |
title | Mathematical modelling of the influence of heat shock proteins on cancer invasion of tissue |
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