TY - JOUR
T1 - MMP-13 In-Vivo molecular imaging reveals early expression in lung adenocarcinoma
AU - Salaün, Mathieu
AU - Peng, Jing
AU - Hensley, Harvey H.
AU - Roder, Navid
AU - Flieder, Douglas B.
AU - Houlle-Crépin, Solène
AU - Abramovici-Roels, Olivia
AU - Sabourin, Jean Christophe
AU - Thiberville, Luc
AU - Clapper, Margie L.
N1 - Publisher Copyright:
© 2015 Salaun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/7/20
Y1 - 2015/7/20
N2 - 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.
AB - 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.
KW - Adenocarcinoma/metabolism
KW - Adenoma/metabolism
KW - Animals
KW - Humans
KW - Immunohistochemistry
KW - Lung Neoplasms/metabolism
KW - Lung/metabolism
KW - Magnetic Resonance Imaging
KW - Matrix Metalloproteinase 13/genetics
KW - Matrix Metalloproteinases/genetics
KW - Mice
KW - Optical Imaging
KW - RNA, Neoplasm/analysis
KW - Real-Time Polymerase Chain Reaction
KW - Tomography, X-Ray Computed
KW - ras Proteins/genetics
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U2 - 10.1371/journal.pone.0132960
DO - 10.1371/journal.pone.0132960
M3 - Article
C2 - 26193700
SN - 1932-6203
VL - 10
SP - e0132960
JO - PLoS ONE
JF - PLoS ONE
IS - 7
M1 - e0132960
ER -