Insulin-like Growth Factor Binding Protein-2 (IGFBP2) Is a Key Molecule in the MACC1-Mediated Platelet Communication and Metastasis of Colorectal Cancer Cells

Tumor cell crosstalk with platelets and, subsequently, their activation are key steps in hematogenous tumor metastasis. MACC1 is an oncogene involved in molecular pathogenesis of colorectal cancer (CRC) and other solid tumor entities, mediating motility and metastasis, making MACC1 an accepted progn...

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Autores principales:	Reza Haschemi, Dennis Kobelt, Elisabeth Steinwarz, Martin Schlesinger, Ulrike Stein, Gerd Bendas
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	colorectal cancer IGFBP2 MACC1 metastasis platelets Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/fd569cdce8bb462493f881e11822584c
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spelling	oai:doaj.org-article:fd569cdce8bb462493f881e11822584c2021-11-25T17:54:13ZInsulin-like Growth Factor Binding Protein-2 (IGFBP2) Is a Key Molecule in the MACC1-Mediated Platelet Communication and Metastasis of Colorectal Cancer Cells10.3390/ijms2222121951422-00671661-6596https://doaj.org/article/fd569cdce8bb462493f881e11822584c2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12195https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Tumor cell crosstalk with platelets and, subsequently, their activation are key steps in hematogenous tumor metastasis. MACC1 is an oncogene involved in molecular pathogenesis of colorectal cancer (CRC) and other solid tumor entities, mediating motility and metastasis, making MACC1 an accepted prognostic biomarker. However, the impact of MACC1 on platelet activation has not yet been addressed. Here, we investigated the activation of platelets by human CRC cells upon MACC1 modulation, indicated by platelet aggregation and granule release. These approaches led to the identification of insulin-like growth factor binding protein-2 (IGFBP2) as a functional downstream molecule of MACC1, affecting communication with platelets. This was confirmed by an shRNA-mediated IGFBP2 knockdown, while maintaining MACC1 activity. Although IGFBP2 displayed an attenuated platelet activation potential, obviously by scavenging IGF-I as a platelet costimulatory mediator, the MACC1/IGFBP2 axis did not affect the thrombin formation potential of the cells. Furthermore, the IGFBP2/MACC1-driven cell migration and invasiveness was further accelerated by platelets. The key role of IGFBP2 for the metastatic spread in vivo was confirmed in a xenograft mouse model. Data provide evidence for IGFBP2 as a downstream functional component of MACC1-driven metastasis, linking these two accepted oncogenic biomarkers for the first time in a platelet context.Reza HaschemiDennis KobeltElisabeth SteinwarzMartin SchlesingerUlrike SteinGerd BendasMDPI AGarticlecolorectal cancerIGFBP2MACC1metastasisplateletsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12195, p 12195 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer IGFBP2 MACC1 metastasis platelets Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	colorectal cancer IGFBP2 MACC1 metastasis platelets Biology (General) QH301-705.5 Chemistry QD1-999 Reza Haschemi Dennis Kobelt Elisabeth Steinwarz Martin Schlesinger Ulrike Stein Gerd Bendas Insulin-like Growth Factor Binding Protein-2 (IGFBP2) Is a Key Molecule in the MACC1-Mediated Platelet Communication and Metastasis of Colorectal Cancer Cells
description	Tumor cell crosstalk with platelets and, subsequently, their activation are key steps in hematogenous tumor metastasis. MACC1 is an oncogene involved in molecular pathogenesis of colorectal cancer (CRC) and other solid tumor entities, mediating motility and metastasis, making MACC1 an accepted prognostic biomarker. However, the impact of MACC1 on platelet activation has not yet been addressed. Here, we investigated the activation of platelets by human CRC cells upon MACC1 modulation, indicated by platelet aggregation and granule release. These approaches led to the identification of insulin-like growth factor binding protein-2 (IGFBP2) as a functional downstream molecule of MACC1, affecting communication with platelets. This was confirmed by an shRNA-mediated IGFBP2 knockdown, while maintaining MACC1 activity. Although IGFBP2 displayed an attenuated platelet activation potential, obviously by scavenging IGF-I as a platelet costimulatory mediator, the MACC1/IGFBP2 axis did not affect the thrombin formation potential of the cells. Furthermore, the IGFBP2/MACC1-driven cell migration and invasiveness was further accelerated by platelets. The key role of IGFBP2 for the metastatic spread in vivo was confirmed in a xenograft mouse model. Data provide evidence for IGFBP2 as a downstream functional component of MACC1-driven metastasis, linking these two accepted oncogenic biomarkers for the first time in a platelet context.
format	article
author	Reza Haschemi Dennis Kobelt Elisabeth Steinwarz Martin Schlesinger Ulrike Stein Gerd Bendas
author_facet	Reza Haschemi Dennis Kobelt Elisabeth Steinwarz Martin Schlesinger Ulrike Stein Gerd Bendas
author_sort	Reza Haschemi
title	Insulin-like Growth Factor Binding Protein-2 (IGFBP2) Is a Key Molecule in the MACC1-Mediated Platelet Communication and Metastasis of Colorectal Cancer Cells
title_short	Insulin-like Growth Factor Binding Protein-2 (IGFBP2) Is a Key Molecule in the MACC1-Mediated Platelet Communication and Metastasis of Colorectal Cancer Cells
title_full	Insulin-like Growth Factor Binding Protein-2 (IGFBP2) Is a Key Molecule in the MACC1-Mediated Platelet Communication and Metastasis of Colorectal Cancer Cells
title_fullStr	Insulin-like Growth Factor Binding Protein-2 (IGFBP2) Is a Key Molecule in the MACC1-Mediated Platelet Communication and Metastasis of Colorectal Cancer Cells
title_full_unstemmed	Insulin-like Growth Factor Binding Protein-2 (IGFBP2) Is a Key Molecule in the MACC1-Mediated Platelet Communication and Metastasis of Colorectal Cancer Cells
title_sort	insulin-like growth factor binding protein-2 (igfbp2) is a key molecule in the macc1-mediated platelet communication and metastasis of colorectal cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fd569cdce8bb462493f881e11822584c
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Insulin-like Growth Factor Binding Protein-2 (IGFBP2) Is a Key Molecule in the MACC1-Mediated Platelet Communication and Metastasis of Colorectal Cancer Cells

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