Live imaging of cysteine-cathepsin activity reveals dynamics of focal inflammation, angiogenesis, and polyp growth Journal Article
| Authors: | Gounaris, E.; Tung, C. H.; Restaino, C.; Maehr, R.; Kohler, R.; Joyce, J. A.; Plough, H. L.; Barrett, T. A.; Weissleder, R.; Khazaie, K. |
| Article Title: | Live imaging of cysteine-cathepsin activity reveals dynamics of focal inflammation, angiogenesis, and polyp growth |
| Abstract: | It has been estimated that up to 30% of detectable polyps in patients regress spontaneously. One major challenge in the evaluation of effective therapy of cancer is the readout for tumor regression and favorable biological response to therapy. Inducible near infra-red (NIR) fluorescent probes were utilized to visualize intestinal polyps of mice hemizygous for a novel truncation of the Adenomatous Polyposis coli (APC) gene. Laser Scanning Confocal Microscopy in live mice allowed visualization of cathepsin activity in richly vascularized benign dysplastic lesions. Using biotinylated suicide inhibitors we quantified increased activities of the Cathepsin B & Z in the polyps. More than 3/4 of the probe signal was localized in CD11b+Gr1+ myeloid derived suppressor cells (MDSC) and CD11b+F4/80+ macrophages infiltrating the lesions. Polyposis was attenuated through genetic ablation of cathepsin B, and suppressed by neutralization of TNFαa in mice. In both cases, diminished probe signal was accounted for by loss of MDSC. Thus, in vivo NIR imaging of focal cathepsin activity reveals inflammatory reactions etiologically linked with cancer progression and is a suitable approach for monitoring response to therapy. © 2008 Gounaris et al. |
| Keywords: | controlled study; genetics; pathogenesis; nonhuman; flow cytometry; animal cell; mouse; animal; metabolism; animals; mice; animal tissue; mus; animal experiment; animal model; inflammation; in vivo study; pathology; enzyme activity; molecular imaging; mice, inbred c57bl; c57bl mouse; disease model; tumor suppressor gene; tumor necrosis factor alpha; drug mechanism; quantitative analysis; cd11b antigen; hemizygosity; cathepsin; cathepsin b; cathepsins; tumor growth; lymphocytic infiltration; disease models, animal; macrophage; macrophages; tumor vascularization; fluorescence analysis; apc protein; suppressor cell; cysteine; confocal laser microscopy; intestine polyp; adenomatous polyposis coli; tumor necrosis factor alpha antibody; suppressor gene; intestinal polyps; colon polyposis; genes, apc; genes, suppressor |
| Journal Title: | PLoS ONE |
| Volume: | 3 |
| Issue: | 8 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2008-08-13 |
| Start Page: | e2916 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0002916 |
| PUBMED: | 18698347 |
| PROVIDER: | scopus |
| PMCID: | PMC2488397 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 17" - "Export Date: 17 November 2011" - "Source: Scopus" |
