Image-based assessment of growth and signaling changes in cancer cells mediated by direct cell-cell contact.

<h4>Background</h4>Many important biological processes are controlled through cell-cell interactions, including the colonization of metastatic tumor cells and the control of differentiation of stem cells within their niche. Despite the crucial importance of the cellular environment in re...

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Autores principales: Peter Lapan, Jing Zhang, Andrew Hill, Ying Zhang, Robert Martinez, Steven Haney
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Publicado: Public Library of Science (PLoS) 2009
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Acceso en línea:https://doaj.org/article/f00d923c6b7d4158b96e1496bf2ee687
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spelling oai:doaj.org-article:f00d923c6b7d4158b96e1496bf2ee6872021-11-25T06:20:38ZImage-based assessment of growth and signaling changes in cancer cells mediated by direct cell-cell contact.1932-620310.1371/journal.pone.0006822https://doaj.org/article/f00d923c6b7d4158b96e1496bf2ee6872009-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19774227/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Many important biological processes are controlled through cell-cell interactions, including the colonization of metastatic tumor cells and the control of differentiation of stem cells within their niche. Despite the crucial importance of the cellular environment in regulating cellular signaling, in vitro methods for the study of such interactions are difficult and/or indirect.<h4>Methodology/principal findings</h4>We report on the development of an image-based method for distinguishing two cell types grown in coculture. Furthermore, cells of one type that are in direct contact with cells of a second type (adjacent cells) can be analyzed separately from cells that are not within a single well. Changes are evaluated using population statistics, which are useful in detecting subtle changes across two populations. We have used this system to characterize changes in the LNCaP prostate carcinoma cell line when grown in contact with human vascular endothelial cells (HUVECs). We find that the expression and phosphorylation of WWOX is reduced in LNCaP cells when grown in direct contact with HUVECs. Reduced WWOX signaling has been associated with reduced activation or expression of JNK and p73. We find that p73 levels are also reduced in LNCaP cells grown in contact with HUVECs, but we did not observe such a change in JNK levels.<h4>Conclusions/significance</h4>We find that the method described is statistically robust and can be adapted to a wide variety of studies where cell function or signaling are affected by heterotypic cell-cell contact. Ironically, a potential challenge to the method is its high level of sensitivity is capable of classifying events as statistically significant (due to the high number cells evaluated individually), when the biological effect may be less clear. The methodology would be best used in conjunction with additional methods to evaluate the biological role of potentially subtle differences between populations. However, many important events, such as the establishment of a metastatic tumor, occur through rare but important changes, and methods such as we describe here can be used to identify and characterize the contribution of the environment to these changes.Peter LapanJing ZhangAndrew HillYing ZhangRobert MartinezSteven HaneyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 8, p e6822 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Peter Lapan
Jing Zhang
Andrew Hill
Ying Zhang
Robert Martinez
Steven Haney
Image-based assessment of growth and signaling changes in cancer cells mediated by direct cell-cell contact.
description <h4>Background</h4>Many important biological processes are controlled through cell-cell interactions, including the colonization of metastatic tumor cells and the control of differentiation of stem cells within their niche. Despite the crucial importance of the cellular environment in regulating cellular signaling, in vitro methods for the study of such interactions are difficult and/or indirect.<h4>Methodology/principal findings</h4>We report on the development of an image-based method for distinguishing two cell types grown in coculture. Furthermore, cells of one type that are in direct contact with cells of a second type (adjacent cells) can be analyzed separately from cells that are not within a single well. Changes are evaluated using population statistics, which are useful in detecting subtle changes across two populations. We have used this system to characterize changes in the LNCaP prostate carcinoma cell line when grown in contact with human vascular endothelial cells (HUVECs). We find that the expression and phosphorylation of WWOX is reduced in LNCaP cells when grown in direct contact with HUVECs. Reduced WWOX signaling has been associated with reduced activation or expression of JNK and p73. We find that p73 levels are also reduced in LNCaP cells grown in contact with HUVECs, but we did not observe such a change in JNK levels.<h4>Conclusions/significance</h4>We find that the method described is statistically robust and can be adapted to a wide variety of studies where cell function or signaling are affected by heterotypic cell-cell contact. Ironically, a potential challenge to the method is its high level of sensitivity is capable of classifying events as statistically significant (due to the high number cells evaluated individually), when the biological effect may be less clear. The methodology would be best used in conjunction with additional methods to evaluate the biological role of potentially subtle differences between populations. However, many important events, such as the establishment of a metastatic tumor, occur through rare but important changes, and methods such as we describe here can be used to identify and characterize the contribution of the environment to these changes.
format article
author Peter Lapan
Jing Zhang
Andrew Hill
Ying Zhang
Robert Martinez
Steven Haney
author_facet Peter Lapan
Jing Zhang
Andrew Hill
Ying Zhang
Robert Martinez
Steven Haney
author_sort Peter Lapan
title Image-based assessment of growth and signaling changes in cancer cells mediated by direct cell-cell contact.
title_short Image-based assessment of growth and signaling changes in cancer cells mediated by direct cell-cell contact.
title_full Image-based assessment of growth and signaling changes in cancer cells mediated by direct cell-cell contact.
title_fullStr Image-based assessment of growth and signaling changes in cancer cells mediated by direct cell-cell contact.
title_full_unstemmed Image-based assessment of growth and signaling changes in cancer cells mediated by direct cell-cell contact.
title_sort image-based assessment of growth and signaling changes in cancer cells mediated by direct cell-cell contact.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/f00d923c6b7d4158b96e1496bf2ee687
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AT jingzhang imagebasedassessmentofgrowthandsignalingchangesincancercellsmediatedbydirectcellcellcontact
AT andrewhill imagebasedassessmentofgrowthandsignalingchangesincancercellsmediatedbydirectcellcellcontact
AT yingzhang imagebasedassessmentofgrowthandsignalingchangesincancercellsmediatedbydirectcellcellcontact
AT robertmartinez imagebasedassessmentofgrowthandsignalingchangesincancercellsmediatedbydirectcellcellcontact
AT stevenhaney imagebasedassessmentofgrowthandsignalingchangesincancercellsmediatedbydirectcellcellcontact
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