Journal article
Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance
Scientific reports, Vol.8(1), pp.14008-10
09/18/2018
DOI: 10.1038/s41598-018-32159-x
PMCID: PMC6143627
PMID: 30228296
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.
Details
- Title: Subtitle
- Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance
- Creators
- Shin-Heng Chiou - Stanford UniversityMadeleine Dorsch - University of Duisburg-EssenEva Kusch - University of Duisburg-EssenSantiago Naranjo - Stanford UniversityMargaret M. Kozak - Stanford UniversityAlbert C. Koong - The University of Texas MD Anderson Cancer CenterMonte M. Winslow - Stanford UniversityBarbara M. Gruener - Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Essen, Germany
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.8(1), pp.14008-10
- DOI
- 10.1038/s41598-018-32159-x
- PMID
- 30228296
- PMCID
- PMC6143627
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Springer Nature
- Number of pages
- 10
- Grant note
- 13-20-25-WINS / Pancreatic Cancer Action Network-AACR Award in memory of Skip Viraugh German Research Foundation (DFG) P30-CA124435 / Stanford Cancer Institute grant from the National Cancer Institute 14-40-25-GRUE / Pancreatic Cancer Action Network - AACR Fellowship in memory of Samuel Stroum P30CA124435 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) HFCR-15-06-07 / Hope Funds for Cancer Research
- Language
- English
- Date published
- 09/18/2018
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984313090902771
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