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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 24, 2013 |
| Title |
Transcriptional effects of CTGF inhibition and gemcitabine in the KPC mouse model of pancreatic ductal adenocarcinoma |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Pancreatic ductal adenocarcinoma (PDA) is characterized by abundant desmoplasia and poor tissue perfusion. These features are proposed to limit access of therapies to neoplastic cells and blunt treatment efficacy. Indeed, several agents that target the PDA microenvironment promote chemotherapy delivery and improve anti-neoplastic responses in murine models of PDA. Here, we employed the FG-3019 monoclonal antibody directed against the pleiotropic matricellular signaling molecule connective tissue growth factor (CTGF/CCN2). FG-3019 treatment increased PDA cell killing and led to a dramatic tumor response without altering gemcitabine delivery. Microarray expression profiling revealed the down-regulation by FG-3019 of several anti-apoptotic transcripts, including the master regulator Xiap, down-regulation of which has been shown to sensitize PDA to gemcitabine. Decreases in XIAP protein by FG-3019 in the presence and absence of gemcitabine were confirmed by immunoblot, while increases in XIAP protein were seen in PDA cell lines treated with recombinant CTGF. Therefore, alterations in survival cues following targeting of tumor microenvironmental factors may play an important role in treatment responses in animal models and, by extension, PDA patients.
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| Overall design |
Total RNA was isolated from KPC mouse PDA tumors 9 days after initiation of treatment with IgG (n=7 biological replicates), FG-3019 (n=5), IgG + gemcitabine (n=6), or FG-3019 + gemcitabine (n=6) and hybridized to Affymetrix 430A 2.0 microarrays. CEL files were processed by GC-RMA and rescaled using median per-gene normalization in GeneSpring GX 7.3.1.
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| Contributor(s) |
Sternlicht MD, Neesse A, Frese KK, Tuveson DA, Seeley TW |
| Citation(s) |
23836645 |
| Submission date |
Apr 18, 2013 |
| Last update date |
May 04, 2018 |
| Contact name |
Mark D. Sternlicht |
| E-mail(s) |
msternlicht@fibrogen.com
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| Phone |
1-415-978-1496
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| Fax |
1-415-978-1908
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| Organization name |
FibroGen, Inc.
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| Department |
Molecular Biology
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| Street address |
409 Illinois Street
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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| Samples (24)
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| GSM1126201 |
IgG treated tumor, biological rep4 |
| GSM1126202 |
IgG treated tumor, biological rep5 |
| GSM1126203 |
IgG treated tumor, biological rep6 |
| GSM1126204 |
IgG treated tumor, biological rep7 |
| GSM1126205 |
FG-3019 treated tumor, biological rep1 |
| GSM1126206 |
FG-3019 treated tumor, biological rep2 |
| GSM1126207 |
FG-3019 treated tumor, biological rep3 |
| GSM1126208 |
FG-3019 treated tumor, biological rep4 |
| GSM1126209 |
FG-3019 treated tumor, biological rep5 |
| GSM1126210 |
IgG + gemcitabine treated tumor, biological rep1 |
| GSM1126211 |
IgG + gemcitabine treated tumor, biological rep2 |
| GSM1126212 |
IgG + gemcitabine treated tumor, biological rep3 |
| GSM1126213 |
IgG + gemcitabine treated tumor, biological rep4 |
| GSM1126214 |
IgG + gemcitabine treated tumor, biological rep5 |
| GSM1126215 |
IgG + gemcitabine treated tumor, biological rep6 |
| GSM1126216 |
FG-3019 + gemcitabine treated tumor, biological rep1 |
| GSM1126217 |
FG-3019 + gemcitabine treated tumor, biological rep2 |
| GSM1126218 |
FG-3019 + gemcitabine treated tumor, biological rep3 |
| GSM1126219 |
FG-3019 + gemcitabine treated tumor, biological rep4 |
| GSM1126220 |
FG-3019 + gemcitabine treated tumor, biological rep5 |
| GSM1126221 |
FG-3019 + gemcitabine treated tumor, biological rep6 |
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| Relations |
| BioProject |
PRJNA198031 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46203_RAW.tar |
49.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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