Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance

Abstract Expression of the chromatin-associated protein HMGA2 correlates with progression, metastasis and therapy resistance in pancreatic ductal adenocarcinoma (PDAC). Hmga2 has also been identified as a marker of a transient subpopulation of PDAC cells that has increased metastatic ability. Here,...

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Autores principales:	Shin-Heng Chiou, Madeleine Dorsch, Eva Kusch, Santiago Naranjo, Margaret M. Kozak, Albert C. Koong, Monte M. Winslow, Barbara M. Grüner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	High Mobility Group A2 (HMGA2) Pancreatic Ductal Adenocarcinoma (PDAC) HMGA2 Protein PDAC Cells Murine PDAC Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b72834b1a36a49d0bfd2fb6d72fac298
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spelling	oai:doaj.org-article:b72834b1a36a49d0bfd2fb6d72fac2982021-12-02T15:08:13ZHmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance10.1038/s41598-018-32159-x2045-2322https://doaj.org/article/b72834b1a36a49d0bfd2fb6d72fac2982018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32159-xhttps://doaj.org/toc/2045-2322Abstract Expression of the chromatin-associated protein HMGA2 correlates with progression, metastasis and therapy resistance in pancreatic ductal adenocarcinoma (PDAC). Hmga2 has also been identified as a marker of a transient subpopulation of PDAC cells that has increased metastatic ability. Here, we characterize the requirement for Hmga2 during growth, dissemination, and metastasis of PDAC in vivo using conditional inactivation of Hmga2 in well-established autochthonous mouse models of PDAC. Overall survival, primary tumour burden, presence of disseminated tumour cells in the peritoneal cavity or circulating tumour cells in the blood, and presence and number of metastases were not significantly different between mice with Hmga2-wildtype or Hmga2-deficient tumours. Treatment of mice with Hmga2-wildtype and Hmga2-deficient tumours with gemcitabine did not uncover a significant impact of Hmga2-deficiency on gemcitabine sensitivity. Hmga1 and Hmga2 overlap in their expression in both human and murine PDAC, however knockdown of Hmga1 in Hmga2-deficient cancer cells also did not decrease metastatic ability. Thus, Hmga2 remains a prognostic marker which identifies a metastatic cancer cell state in primary PDAC, however Hmga2 has limited if any direct functional impact on PDAC progression and therapy resistance.Shin-Heng ChiouMadeleine DorschEva KuschSantiago NaranjoMargaret M. KozakAlbert C. KoongMonte M. WinslowBarbara M. GrünerNature PortfolioarticleHigh Mobility Group A2 (HMGA2)Pancreatic Ductal Adenocarcinoma (PDAC)HMGA2 ProteinPDAC CellsMurine PDACMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	High Mobility Group A2 (HMGA2) Pancreatic Ductal Adenocarcinoma (PDAC) HMGA2 Protein PDAC Cells Murine PDAC Medicine R Science Q
spellingShingle	High Mobility Group A2 (HMGA2) Pancreatic Ductal Adenocarcinoma (PDAC) HMGA2 Protein PDAC Cells Murine PDAC Medicine R Science Q Shin-Heng Chiou Madeleine Dorsch Eva Kusch Santiago Naranjo Margaret M. Kozak Albert C. Koong Monte M. Winslow Barbara M. Grüner Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance
description	Abstract Expression of the chromatin-associated protein HMGA2 correlates with progression, metastasis and therapy resistance in pancreatic ductal adenocarcinoma (PDAC). Hmga2 has also been identified as a marker of a transient subpopulation of PDAC cells that has increased metastatic ability. Here, we characterize the requirement for Hmga2 during growth, dissemination, and metastasis of PDAC in vivo using conditional inactivation of Hmga2 in well-established autochthonous mouse models of PDAC. Overall survival, primary tumour burden, presence of disseminated tumour cells in the peritoneal cavity or circulating tumour cells in the blood, and presence and number of metastases were not significantly different between mice with Hmga2-wildtype or Hmga2-deficient tumours. Treatment of mice with Hmga2-wildtype and Hmga2-deficient tumours with gemcitabine did not uncover a significant impact of Hmga2-deficiency on gemcitabine sensitivity. Hmga1 and Hmga2 overlap in their expression in both human and murine PDAC, however knockdown of Hmga1 in Hmga2-deficient cancer cells also did not decrease metastatic ability. Thus, Hmga2 remains a prognostic marker which identifies a metastatic cancer cell state in primary PDAC, however Hmga2 has limited if any direct functional impact on PDAC progression and therapy resistance.
format	article
author	Shin-Heng Chiou Madeleine Dorsch Eva Kusch Santiago Naranjo Margaret M. Kozak Albert C. Koong Monte M. Winslow Barbara M. Grüner
author_facet	Shin-Heng Chiou Madeleine Dorsch Eva Kusch Santiago Naranjo Margaret M. Kozak Albert C. Koong Monte M. Winslow Barbara M. Grüner
author_sort	Shin-Heng Chiou
title	Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance
title_short	Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance
title_full	Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance
title_fullStr	Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance
title_full_unstemmed	Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance
title_sort	hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/b72834b1a36a49d0bfd2fb6d72fac298
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Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance

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