Journal Article
. 2007 Jan; 67(1):139-48.
doi: 10.1158/0008-5472.CAN-06-2563.

Gene expression profile of metastatic human pancreatic cancer cells depends on the organ microenvironment

Toru Nakamura 1 Isaiah J Fidler  Kevin R Coombes  
Affiliations
  • PMID: 17210693
  •     43 citations

Abstract

To determine the influence of the microenvironment on changes in gene expression, we did microarray analysis on three variant lines of a human pancreatic cancer (FG, L3.3, and L3.6pl) with different metastatic potentials. The variant lines were grown in tissue culture in the subcutis (ectopic) or pancreas (orthotopic) of nude mice. Compared with tissue culture, the number of genes of which the expression was affected by the microenvironment was up-regulated in tumors growing in the subcutis and pancreas. In addition, highly metastatic L3.6pl cells growing in the pancreas expressed significantly higher levels of 226 genes than did the L3.3 or FG variant cells. Growth of the variant lines in the subcutis did not yield similar results, indicating that the orthotopic microenvironment significantly influences gene expression in pancreatic cancer cells. These data suggest that investigations of the functional consequence of gene expression require accounting for experimental growth conditions.

Gene expression profiling of liver metastases and tumour invasion in pancreatic cancer using an orthotopic SCID mouse model.
M Niedergethmann, F Alves, +8 authors, N Gretz.
Br J Cancer, 2007 Oct 18; 97(10). PMID: 17940512    Free PMC article.
Biological characterization of two xenografts derived from human CUPs (carcinomas of unknown primary).
Delphine Lequin, Karim Fizazi, +6 authors, Pierre Busson.
BMC Cancer, 2007 Dec 20; 7. PMID: 18088404    Free PMC article.
Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice.
Archana Thakur, Aliccia Bollig, Jiusheng Wu, Dezhong J Liao.
Mol Cancer, 2008 Jan 26; 7. PMID: 18218118    Free PMC article.
Activation of Wnt signalling in stroma from pancreatic cancer identified by gene expression profiling.
Christian Pilarsky, Ole Ammerpohl, +18 authors, Robert Grützmann.
J Cell Mol Med, 2008 Feb 27; 12(6B). PMID: 18298655    Free PMC article.
Biochemical constitution of extracellular medium is critical for control of human breast cancer MDA-MB-231 cell motility.
Huiyan Pan, Mustafa B A Djamgoz.
J Membr Biol, 2008 Jun 26; 223(1). PMID: 18575796
Dynamic imaging of cancer growth and invasion: a modified skin-fold chamber model.
Stephanie Alexander, Gudrun E Koehl, +2 authors, Peter Friedl.
Histochem Cell Biol, 2008 Nov 07; 130(6). PMID: 18987875
Highly Cited.
An orthotopic murine model of sinonasal malignancy.
Alexander Gelbard, Michael E Kupferman, +4 authors, Ehab Y Hanna.
Clin Cancer Res, 2008 Nov 18; 14(22). PMID: 19010850    Free PMC article.
Comparative analysis of metastasis variants derived from human prostate carcinoma cells: roles in intravasation of VEGF-mediated angiogenesis and uPA-mediated invasion.
Erin M Conn, Kenneth A Botkjaer, +3 authors, James P Quigley.
Am J Pathol, 2009 Sep 05; 175(4). PMID: 19729488    Free PMC article.
Differential roles of cyclin D1 and D3 in pancreatic ductal adenocarcinoma.
Nikolina Radulovich, Nhu-An Pham, +4 authors, Ming-Sound Tsao.
Mol Cancer, 2010 Feb 02; 9. PMID: 20113529    Free PMC article.
Phenotype and genotype of pancreatic cancer cell lines.
Emily L Deer, Jessica González-Hernández, +5 authors, Sean J Mulvihill.
Pancreas, 2010 Apr 27; 39(4). PMID: 20418756    Free PMC article.
Highly Cited. Review.
Preclinical development of molecular-targeted agents for cancer.
Alberto Ocana, Atanasio Pandiella, Lillian L Siu, Ian F Tannock.
Nat Rev Clin Oncol, 2010 Dec 08; 8(4). PMID: 21135887
Review.
Metabolomics of gastric cancer metastasis detected by gas chromatography and mass spectrometry.
Jin-Lian Chen, Hui-Qing Tang, +3 authors, Jian-Zhong Gu.
World J Gastroenterol, 2010 Dec 15; 16(46). PMID: 21155010    Free PMC article.
Expression of osteopontin coregulators in primary colorectal cancer and associated liver metastases.
D J Mole, C O'Neill, +6 authors, F C Campbell.
Br J Cancer, 2011 Feb 24; 104(6). PMID: 21343932    Free PMC article.
Selection of brain metastasis-initiating breast cancer cells determined by growth on hard agar.
Lixia Guo, Dominic Fan, +5 authors, Robert R Langley.
Am J Pathol, 2011 Apr 26; 178(5). PMID: 21514446    Free PMC article.
SMYD3 promotes cancer invasion by epigenetic upregulation of the metalloproteinase MMP-9.
Alicia M Cock-Rada, Souhila Medjkane, +6 authors, Jonathan B Weitzman.
Cancer Res, 2011 Dec 24; 72(3). PMID: 22194464    Free PMC article.
Development of a novel preclinical pancreatic cancer research model: bioluminescence image-guided focal irradiation and tumor monitoring of orthotopic xenografts.
Richard Tuli, Andrew Surmak, +9 authors, Joseph M Herman.
Transl Oncol, 2012 Apr 13; 5(2). PMID: 22496923    Free PMC article.
Capture, release and culture of circulating tumor cells from pancreatic cancer patients using an enhanced mixing chip.
Weian Sheng, Olorunseun O Ogunwobi, +4 authors, Z Hugh Fan.
Lab Chip, 2013 Nov 14; 14(1). PMID: 24220648    Free PMC article.
Highly Cited.
Telomerase inhibitor Imetelstat (GRN163L) limits the lifespan of human pancreatic cancer cells.
Katrina M Burchett, Ying Yan, Michel M Ouellette.
PLoS One, 2014 Jan 11; 9(1). PMID: 24409321    Free PMC article.
Co-implanting orthotopic tissue creates stroma microenvironment enhancing growth and angiogenesis of multiple tumors.
Per Borgstrom, Phil Oh, +2 authors, Jan E Schnitzer.
F1000Res, 2013 Jan 01; 2. PMID: 24715954    Free PMC article.
Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages--strategies for data mining in support of therapeutic studies.
Melinda G Hollingshead, Luke H Stockwin, +15 authors, Jerry Collins.
BMC Genomics, 2014 Jun 03; 15. PMID: 24885658    Free PMC article.
[Advances of histone methyltransferase SMYD3 in tumors].
Shangwen Dong, Peng Zhang.
Zhongguo Fei Ai Za Zhi, 2014 Sep 25; 17(9). PMID: 25248712    Free PMC article.
Review.
Targeting Pancreatic Cancer Metastasis by Inhibition of Vav1, a Driver of Tumor Cell Invasion.
Gina L Razidlo, Christopher Magnine, +5 authors, Mark A McNiven.
Cancer Res, 2015 May 16; 75(14). PMID: 25977335    Free PMC article.
Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention.
Aeson Chang, Corina Kim-Fuchs, +2 authors, Erica K Sloan.
Cancers (Basel), 2015 Jul 21; 7(3). PMID: 26193320    Free PMC article.
Review.
Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models.
Daniel L J Thorek, Robin M Kramer, +10 authors, James Russell.
Int J Radiat Oncol Biol Phys, 2015 Aug 05; 93(2). PMID: 26238952    Free PMC article.
Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes.
David Castel, Cathy Philippe, +16 authors, Marie-Anne Debily.
Acta Neuropathol, 2015 Sep 25; 130(6). PMID: 26399631    Free PMC article.
Highly Cited.
A novel method for RNA extraction from FFPE samples reveals significant differences in biomarker expression between orthotopic and subcutaneous pancreatic cancer patient-derived xenografts.
Malachia Hoover, Yvess Adamian, +10 authors, Jonathan A Kelber.
Oncotarget, 2016 Sep 08; 8(4). PMID: 27602776    Free PMC article.
The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer.
Angela M Krebs, Julia Mitschke, +13 authors, Thomas Brabletz.
Nat Cell Biol, 2017 Apr 18; 19(5). PMID: 28414315
Highly Cited.
Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation.
Shoki Sato, Toru Nakamura, +15 authors, Satoshi Hirano.
Oncotarget, 2018 Jan 27; 8(69). PMID: 29371937    Free PMC article.
Tissue-Dependent Tumor Microenvironments and Their Impact on Immunotherapy Responses.
Amanda J Oliver, Peter K H Lau, +4 authors, Clare Y Slaney.
Front Immunol, 2018 Feb 16; 9. PMID: 29445373    Free PMC article.
Review.
Integrated analysis of tumor differentiation genes in pancreatic adenocarcinoma.
Ting Xi, Guizhi Zhang.
PLoS One, 2018 Mar 30; 13(3). PMID: 29596435    Free PMC article.
Orthotopic and heterotopic murine models of pancreatic cancer and their different responses to FOLFIRINOX chemotherapy.
Derek J Erstad, Mozhdeh Sojoodi, +9 authors, Bryan C Fuchs.
Dis Model Mech, 2018 Jun 16; 11(7). PMID: 29903803    Free PMC article.
Effect of Adenomatous Polyposis Coli Loss on Tumorigenic Potential in Pancreatic Ductal Adenocarcinoma.
Jennifer M Cole, Kaitlyn Simmons, Jenifer R Prosperi.
Cells, 2019 Sep 22; 8(9). PMID: 31540078    Free PMC article.
Tissue-specific tumor microenvironments influence responses to immunotherapies.
Amanda J Oliver, Ashleigh S Davey, +9 authors, Clare Y Slaney.
Clin Transl Immunology, 2019 Nov 27; 8(11). PMID: 31768254    Free PMC article.
Epithelial to mesenchymal plasticity and differential response to therapies in pancreatic ductal adenocarcinoma.
Rebecca L Porter, Neelima K C Magnus, +27 authors, David T Ting.
Proc Natl Acad Sci U S A, 2019 Dec 18;. PMID: 31843922    Free PMC article.
SMYD3: An Oncogenic Driver Targeting Epigenetic Regulation and Signaling Pathways.
Cinzia Bottino, Alessia Peserico, Cristiano Simone, Giuseppina Caretti.
Cancers (Basel), 2020 Jan 16; 12(1). PMID: 31935919    Free PMC article.
Review.
Combined Targeting of G9a and Checkpoint Kinase 1 Synergistically Inhibits Pancreatic Cancer Cell Growth by Replication Fork Collapse.
Guillermo Urrutia, Ann Salmonson, +6 authors, Gwen Lomberk.
Mol Cancer Res, 2019 Dec 12; 18(3). PMID: 31822519    Free PMC article.
DeltaNp63-dependent super enhancers define molecular identity in pancreatic cancer by an interconnected transcription factor network.
Feda H Hamdan, Steven A Johnsen.
Proc Natl Acad Sci U S A, 2018 Dec 14; 115(52). PMID: 30541891    Free PMC article.
SMYD3 promotes the epithelial-mesenchymal transition in breast cancer.
Claudio Fenizia, Cinzia Bottino, +7 authors, Giuseppina Caretti.
Nucleic Acids Res, 2018 Dec 14; 47(3). PMID: 30544196    Free PMC article.
Therapeutic efficacy, pharmacokinetic profiles, and toxicological activities of humanized antibody-drug conjugate Zt/g4-MMAE targeting RON receptor tyrosine kinase for cancer therapy.
Hang-Ping Yao, Liang Feng, +9 authors, Ming-Hai Wang.
J Immunother Cancer, 2019 Mar 16; 7(1). PMID: 30871619    Free PMC article.
Cellular plasticity and metastasis in breast cancer: a pre- and post-malignant problem.
Jacob M Smigiel, Sarah E Taylor, +3 authors, Mark W Jackson.
J Cancer Metastasis Treat, 2019 Jan 01; 5. PMID: 32355893    Free PMC article.
Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune regulatory pathways.
Won Jin Ho, Rossin Erbe, +16 authors, Elana J Fertig.
Genome Biol, 2021 May 15; 22(1). PMID: 33985562    Free PMC article.
Murine Macrophages Modulate Their Inflammatory Profile in Response to Gas Plasma-Inactivated Pancreatic Cancer Cells.
Aydar Khabipov, Eric Freund, +6 authors, Sander Bekeschus.
Cancers (Basel), 2021 Jun 03; 13(11). PMID: 34064000    Free PMC article.
Anticancer Effect of Heparin-Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer.
Hae Hyun Hwang, Hee Jeong Jeong, +4 authors, Dong Yun Lee.
Cancers (Basel), 2021 Nov 28; 13(22). PMID: 34830928    Free PMC article.