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Salaun M , Peng J , Hensley HH , Roder N , Flieder DB , Houlle-Crepin S , Abramovici-Roels O , Sabourin JC , Thiberville L , Clapper ML
MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma
PLoS One. 2015 ;10(7) :e0132960
PMID: 26193700    PMCID: PMC4508003    URL: http://www.ncbi.nlm.nih.gov/pubmed/26193700
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INTRODUCTION: Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. OBJECTIVE: To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. METHODS: K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. RESULTS: In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). CONCLUSION: MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer.
Salaun, Mathieu Peng, Jing Hensley, Harvey H Roder, Navid Flieder, Douglas B Houlle-Crepin, Solene Abramovici-Roels, Olivia Sabourin, Jean-Christophe Thiberville, Luc Clapper, Margie L United States PLoS One. 2015 Jul 20;10(7):e0132960. doi: 10.1371/journal.pone.0132960. eCollection 2015.