PMID- 30197480
OWN - NLM
STAT- MEDLINE
DCOM- 20181114
LR  - 20181114
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Print)
IS  - 1007-9327 (Linking)
VI  - 24
IP  - 33
DP  - 2018 Sep 7
TI  - Establishment, functional and genetic characterization of a colon derived large 
      cell neuroendocrine carcinoma cell line.
PG  - 3749-3759
LID - 10.3748/wjg.v24.i33.3749 [doi]
AB  - AIM: To establish cell line and patient-derived xenograft (PDX) models for 
      neuroendocrine carcinomas (NEC) which is highly desirable for gaining insight 
      into tumor development as well as preclinical research including biomarker 
      testing and drug response prediction. METHODS: Cell line establishment was 
      conducted from direct in vitro culturing of colonic NEC tissue (HROC57). A PDX 
      could also successfully be established from vitally frozen tumor samples. 
      Morphological features, invasive and migratory behavior of the HROC57 cells as 
      well as expression of neuroendocrine markers were vastly analyzed. Phenotypic 
      analysis was done by microscopy and multicolor flow cytometry. The extensive 
      molecular-pathological profiling included mutation analysis, assessment of 
      chromosomal and microsatellite instability; and in addition, fingerprinting 
      (i.e., STR analysis) was performed from the cell line in direct comparison to 
      primary patient-derived tissues and the PDX model established. Drug 
      responsiveness was examined for a panel of chemotherapeutics in clinical use for 
      the treatment of solid cancers. RESULTS: The established cell line HROC57 showed 
      distinct morphological and molecular features of a poorly differentiated 
      large-cell NEC with KI-67 > 50%. Molecular-pathological analysis revealed a CpG 
      island promoter methylation positive cell line with microsatellite instability 
      being absent. The following mutation profile was observed: KRAS (wt), BRAF (mut). 
      A high sensitivity to etoposide, cisplatin and 5-FU could be demonstrated while 
      it was more resistant towards rapamycin. CONCLUSION: We successfully established 
      and characterized a novel patient-derived NEC cell line in parallel to a PDX 
      model as a useful tool for further analysis of the biological characteristics and 
      for development of novel diagnostic and therapeutic options for NEC.
FAU - Gock, Michael
AU  - Gock M
AD  - Department of General Surgery, University of Rostock, Rostock 18055, Germany.
FAU - Mullins, Christina S
AU  - Mullins CS
AD  - Department of General Surgery, Section of Molecular Oncology and Immunotherapy, 
      University of Rostock, Rostock 18055, Germany.
FAU - Harnack, Christine
AU  - Harnack C
AD  - Department of General Surgery, Section of Molecular Oncology and Immunotherapy, 
      University of Rostock, Rostock 18055, Germany.
FAU - Prall, Friedrich
AU  - Prall F
AD  - Institute of Pathology, University of Rostock, Rostock 18055, Germany.
FAU - Ramer, Robert
AU  - Ramer R
AD  - Institute of Pharmacology, University of Rostock, Rostock 18055, Germany.
FAU - Goder, Anja
AU  - Goder A
AD  - Institute of Toxicology, University Medical Center Mainz, Mainz 55131, Germany.
FAU - Kramer, Oliver H
AU  - Kramer OH
AD  - Institute of Toxicology, University Medical Center Mainz, Mainz 55131, Germany.
FAU - Klar, Ernst
AU  - Klar E
AD  - Department of General Surgery, University of Rostock, Rostock 18055, Germany.
FAU - Linnebacher, Michael
AU  - Linnebacher M
AD  - Department of General Surgery, Section of Molecular Oncology and Immunotherapy, 
      University of Rostock, Rostock 18055, Germany. 
      michael.linnebacher@med.uni-rostock.de.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Carcinoma, Large Cell/genetics/*pathology/surgery
MH  - Carcinoma, Neuroendocrine/genetics/*pathology/surgery
MH  - Cell Culture Techniques/*methods
MH  - Cell Line, Tumor/drug effects/metabolism/*pathology
MH  - Cell Movement/genetics
MH  - Colon/*pathology/surgery
MH  - CpG Islands/genetics
MH  - DNA Fingerprinting
MH  - DNA Methylation/genetics
MH  - DNA Mutational Analysis
MH  - Drug Resistance, Neoplasm/genetics
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Mutation
MH  - Neoplasm Invasiveness/genetics/pathology
MH  - Primary Cell Culture
MH  - Xenograft Model Antitumor Assays
PMC - PMC6127660
OTO - NOTNLM
OT  - Individualized medicine
OT  - Large cell neuroendocrine carcinoma
OT  - Patient-derived tumor model
COIS- Conflict-of-interest statement: To the best of our knowledge, no conflict of 
      interest exists.
EDAT- 2018/09/11 06:00
MHDA- 2018/11/15 06:00
PMCR- 2018/09/07
CRDT- 2018/09/11 06:00
PHST- 2018/02/28 00:00 [received]
PHST- 2018/06/14 00:00 [revised]
PHST- 2018/06/16 00:00 [accepted]
PHST- 2018/09/11 06:00 [entrez]
PHST- 2018/09/11 06:00 [pubmed]
PHST- 2018/11/15 06:00 [medline]
PHST- 2018/09/07 00:00 [pmc-release]
AID - 10.3748/wjg.v24.i33.3749 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2018 Sep 7;24(33):3749-3759. doi: 
      10.3748/wjg.v24.i33.3749.