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

Scientific Reports

Monte M. Winslow¹  Shin-Heng Chiou¹  Santiago Naranjo¹  Barbara M. Grüner²  Eva Kusch²  Madeleine Dorsch²  Albert C. Koong³  Margaret M. Kozak³ 

[1] Department of Genetics, Stanford University School of Medicine;Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen;Department of Radiation Oncology, Stanford University School of Medicine;

关键词: High Mobility Group A2 (HMGA2);    Pancreatic Ductal Adenocarcinoma (PDAC);    HMGA2 Protein;    PDAC Cells;    Murine PDAC;   

DOI  :  10.1038/s41598-018-32159-x

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown