MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma
Mathieu Salaün1, Jing Peng2, Harvey H Hensley3
1Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America; Laboratoire Quant.I.F - LITIS, EA 4108, Rouen University, Rouen, France; Clinique Pneumologique & CIC INSERM U1404, Rouen University Hospital, Rouen, France.
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.
