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Intracellular Signal‐transducing Elements Involved in Transendothelial Migration of Lymphoma Cells

To investigate the molecular mechanisms underlying transendothelial migration of tumor cells, an essential process for their hematogenous dissemination, we developed an in vitro model system that allows the separate monitoring of cell adhesion and transmigration processes. This system uses a human p...

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Autores principales: Tsuzuki, Shinobu, Toyama‐Sorimachi, Noriko, Kitamura, Fujiko, Tsuboi, Hiroko, Ando, Joji, Sakurai, Takashi, Morii, Narito, Narumiya, Shuh, Miyasaka, Masayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921854/
https://www.ncbi.nlm.nih.gov/pubmed/9685862
http://dx.doi.org/10.1111/j.1349-7006.1998.tb03299.x
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author Tsuzuki, Shinobu
Toyama‐Sorimachi, Noriko
Kitamura, Fujiko
Tsuboi, Hiroko
Ando, Joji
Sakurai, Takashi
Morii, Narito
Narumiya, Shuh
Miyasaka, Masayuki
author_facet Tsuzuki, Shinobu
Toyama‐Sorimachi, Noriko
Kitamura, Fujiko
Tsuboi, Hiroko
Ando, Joji
Sakurai, Takashi
Morii, Narito
Narumiya, Shuh
Miyasaka, Masayuki
author_sort Tsuzuki, Shinobu
collection PubMed
description To investigate the molecular mechanisms underlying transendothelial migration of tumor cells, an essential process for their hematogenous dissemination, we developed an in vitro model system that allows the separate monitoring of cell adhesion and transmigration processes. This system uses a human pre‐B lymphoma cell line, Nalm‐6, and a cultured mouse endothelial cell line, KOP2.16. Nalm‐6 cells rapidly adhered to KOP2.16 and subsequently transmigrated underneath them. Using this model, we examined the effects on transendothelial migration, of various reagents which specifically interfere with the function of intracellular signal transduction molecules. Treatment of Nalm‐6 cells with wortmannin (WMN), herbimycin A, pertussis toxin, or C3 exoenzyme of Clostridium botulinum, which specifically inhibit P13 kinase and/or myosin light chain kinase, herbimycin‐sensitive tyrosine kinases, heterotrimeric G proteins, and the small G proteins rho/rac, respectively, reduced transmigration in a dose‐dependent manner. Pretreatment of KOP2.16 endothelial cells with WMN also reduced transmigration in a dose‐dependent manner. Binding of Nalm‐6 to KOP2.16 was not affected, even when Nalm‐6 or KOP2.16 cells were pretreated with these inhibitors, indicating that the reduction of transmigration was not due to a reduction of Nalm‐6 binding to KOP2.16. These results also indicate that the signal transduction pathway(s) involved in transmigration can be dissociated from that of adhesion. Our results support the notion that endothelial cells are not a passive barrier in lymphoma extravasation, but that they assist lymphoma cell extravasation.
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spelling pubmed-59218542018-05-11 Intracellular Signal‐transducing Elements Involved in Transendothelial Migration of Lymphoma Cells Tsuzuki, Shinobu Toyama‐Sorimachi, Noriko Kitamura, Fujiko Tsuboi, Hiroko Ando, Joji Sakurai, Takashi Morii, Narito Narumiya, Shuh Miyasaka, Masayuki Jpn J Cancer Res Article To investigate the molecular mechanisms underlying transendothelial migration of tumor cells, an essential process for their hematogenous dissemination, we developed an in vitro model system that allows the separate monitoring of cell adhesion and transmigration processes. This system uses a human pre‐B lymphoma cell line, Nalm‐6, and a cultured mouse endothelial cell line, KOP2.16. Nalm‐6 cells rapidly adhered to KOP2.16 and subsequently transmigrated underneath them. Using this model, we examined the effects on transendothelial migration, of various reagents which specifically interfere with the function of intracellular signal transduction molecules. Treatment of Nalm‐6 cells with wortmannin (WMN), herbimycin A, pertussis toxin, or C3 exoenzyme of Clostridium botulinum, which specifically inhibit P13 kinase and/or myosin light chain kinase, herbimycin‐sensitive tyrosine kinases, heterotrimeric G proteins, and the small G proteins rho/rac, respectively, reduced transmigration in a dose‐dependent manner. Pretreatment of KOP2.16 endothelial cells with WMN also reduced transmigration in a dose‐dependent manner. Binding of Nalm‐6 to KOP2.16 was not affected, even when Nalm‐6 or KOP2.16 cells were pretreated with these inhibitors, indicating that the reduction of transmigration was not due to a reduction of Nalm‐6 binding to KOP2.16. These results also indicate that the signal transduction pathway(s) involved in transmigration can be dissociated from that of adhesion. Our results support the notion that endothelial cells are not a passive barrier in lymphoma extravasation, but that they assist lymphoma cell extravasation. Blackwell Publishing Ltd 1998-05 /pmc/articles/PMC5921854/ /pubmed/9685862 http://dx.doi.org/10.1111/j.1349-7006.1998.tb03299.x Text en
spellingShingle Article
Tsuzuki, Shinobu
Toyama‐Sorimachi, Noriko
Kitamura, Fujiko
Tsuboi, Hiroko
Ando, Joji
Sakurai, Takashi
Morii, Narito
Narumiya, Shuh
Miyasaka, Masayuki
Intracellular Signal‐transducing Elements Involved in Transendothelial Migration of Lymphoma Cells
title Intracellular Signal‐transducing Elements Involved in Transendothelial Migration of Lymphoma Cells
title_full Intracellular Signal‐transducing Elements Involved in Transendothelial Migration of Lymphoma Cells
title_fullStr Intracellular Signal‐transducing Elements Involved in Transendothelial Migration of Lymphoma Cells
title_full_unstemmed Intracellular Signal‐transducing Elements Involved in Transendothelial Migration of Lymphoma Cells
title_short Intracellular Signal‐transducing Elements Involved in Transendothelial Migration of Lymphoma Cells
title_sort intracellular signal‐transducing elements involved in transendothelial migration of lymphoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921854/
https://www.ncbi.nlm.nih.gov/pubmed/9685862
http://dx.doi.org/10.1111/j.1349-7006.1998.tb03299.x
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