Document Detail


KISS1 over-expression suppresses metastasis of pancreatic adenocarcinoma in a xenograft mouse model.
MedLine Citation:
PMID:  20844932     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Identifying molecular targets for treatment of pancreatic cancer metastasis is critical due to the high frequency of dissemination prior to diagnosis of this lethal disease. Because the KISS1 metastasis suppressor is expressed at reduced levels in advanced pancreatic cancer, we hypothesized that re-expression of KISS1 would reduce metastases. Highly metastatic S2VP10 cells expressing luciferase (S2VP10L) were transfected with a FLAG-tagged version of KISS1 (KFM), KFMΔSS (with deleted secretion signal sequence), or pcDNA3 control plasmid (CP) and expression was confirmed by RTQ-PCR. SCID mice were implanted orthotopically with S2VP10L cells or transfectants and tumor growth and metastases were monitored using bioluminescence imaging. Mice with S2VP10L-KISS1 tumors developed fewer liver (98%) and lung (99%) metastases than S2VP10L. Unexpectedly, mice with S2VP10L-KFMΔSS tumors also had reduced liver and lung metastases, but had more metastases than mice with S2VP10L-KISS. KISS1 protein was found in the cytoplasm of both KFMΔSS and KISS1-expressing orthotopic tumors by immunohistochemistry. Metastases were not found in lungs of mice with S2VP10L-KISS1 tumors; whereas, KFMΔSS lung sections had regions of concentrated KISS1 staining, suggesting that secretion of KISS1 is needed to reduce metastasis significantly. These data suggest induction of KISS1 expression has potential as an adjuvant treatment for pancreatic cancer.
Authors:
Lacey R McNally; Danny R Welch; Benjamin H Beck; Lewis J Stafford; Joshua W Long; Jeffery C Sellers; Zhi Q Huang; William E Grizzle; Cecil R Stockard; Kevin T Nash; Donald J Buchsbaum
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-16
Journal Detail:
Title:  Clinical & experimental metastasis     Volume:  27     ISSN:  1573-7276     ISO Abbreviation:  Clin. Exp. Metastasis     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-03     Completed Date:  2010-12-20     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  8409970     Medline TA:  Clin Exp Metastasis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  591-600     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics*,  pathology,  secondary*
Animals
Disease Models, Animal
Gene Expression
Gene Expression Profiling
Humans
Kisspeptins
Liver Neoplasms / secondary
Lung Neoplasms / secondary
Mice
Neoplasm Metastasis / genetics
Neoplasm Transplantation
Neoplasms, Experimental / genetics,  pathology,  secondary
Pancreatic Neoplasms / genetics*,  pathology*
Reverse Transcriptase Polymerase Chain Reaction
Transplantation, Heterologous
Tumor Cells, Cultured
Tumor Suppressor Proteins / genetics*,  metabolism*
Xenograft Model Antitumor Assays*
Grant Support
ID/Acronym/Agency:
1K99CA139050/CA/NCI NIH HHS; CA134981/CA/NCI NIH HHS; CA87728/CA/NCI NIH HHS; K99 CA139050/CA/NCI NIH HHS; K99 CA139050-01/CA/NCI NIH HHS; P20 CA101955/CA/NCI NIH HHS; P20 CA101955-01/CA/NCI NIH HHS; P20 CA101955-010003/CA/NCI NIH HHS; P20 CA101955-05/CA/NCI NIH HHS; P20CA101955/CA/NCI NIH HHS; P30 CA013148/CA/NCI NIH HHS; P30 CA013148-38/CA/NCI NIH HHS; P30CA013148/CA/NCI NIH HHS; P50 CA101955/CA/NCI NIH HHS; R01 CA087728/CA/NCI NIH HHS; R01 CA087728-09S1/CA/NCI NIH HHS; R01 CA134981/CA/NCI NIH HHS; R01 CA134981-03/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/KISS1 protein, human; 0/Kisspeptins; 0/Tumor Suppressor Proteins
Comments/Corrections

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