Multimodality imaging of TGFβ signaling in breast cancer metastases Journal Article
| Authors: | Serganova, I.; Moroz, E.; Vider, J.; Gogiberidze, G.; Moroz, M.; Pillarsetty, N.; Doubrovin, M.; Minn, A.; Thaler, H. T.; Massague, J.; Gelovani, J.; Blasberg, R. |
| Article Title: | Multimodality imaging of TGFβ signaling in breast cancer metastases |
| Abstract: | The skeleton is a preferred site for breast cancer metastasis. We have developed a multimodality imaging approach to monitor the transforming growth factor β (TGFβ) signaling pathway in bone metastases, sequentially over time in the same animal. As model systems, two MDA-MB-231 breast cancer cells lines with different metastatic tropisms, SCP2 and SCP3, were transduced with constitutive and TGFβ-inducible reporter genes and were tested in vitro and in living animals. The sites and expansion of metastases were visualized by bioluminescence imaging using a constitutive firefly luciferase reporter, while TGFβ signaling in metastases was monitored by microPET imaging of HSV1-TK/GFP expression with [<sup>18</sup>F]FEAU and by a more sensitive and cost-effective bioluminescence reporter, based on nonsecreted Gaussia luciferase. Concurrent and sequential imaging of metastases in the same animals provided insight into the location and progression of metastases, and the timing and course of TGFβ signaling. The anticipated and newly observed differences in the imaging of tumors from two related cell lines have demonstrated that TGFβ signal transduction pathway activity can be noninvasively imaged with high sensitivity and reproducibility, thereby providing the opportunity for an assessment of novel treatments that target TGFβ signaling. © FASEB. |
| Keywords: | signal transduction; protein expression; bone neoplasms; bone tumor; unclassified drug; human cell; genetics; cancer growth; nonhuman; bone metastasis; molecular genetics; positron emission tomography; diagnostic accuracy; reproducibility; monitoring; mouse; animal; metabolism; animals; mice; animal tissue; metastasis; computer assisted tomography; transforming growth factor beta; green fluorescent protein; animal experiment; animal model; tomography, x-ray computed; cancer cell culture; in vitro study; cell line, tumor; breast neoplasms; animalia; cost effectiveness analysis; molecular sequence data; diagnostic agent; xenograft; nude mouse; mice, nude; nucleotide sequence; breast tumor; recombinant proteins; recombinant protein; tumor cell line; positron-emission tomography; simplexvirus; reporter gene; transplantation, heterologous; base sequence; green fluorescent proteins; genes, reporter; radioisotope; neoplasm transplantation; breast adenocarcinoma; non invasive procedure; bioluminescence; complementary dna; spine metastasis; feau; dna, complementary; introspection; firefly luciferase; bone resorption; herpes simplex virus type one thymidine kinase; smads complex; 5 ethyl 2' fluorouracil arabinoside; 5 ethyl 2' fluorouracil arabinoside f 18; coelenterazine; fialuridine c 14; thymidine h 3; adrenal metastasis; hsv1 tk gene; cancer transplantation; luciferases, firefly |
| Journal Title: | FASEB Journal |
| Volume: | 23 |
| Issue: | 8 |
| ISSN: | 0892-6638 |
| Publisher: | Federation of American Societies for Experimental Biology |
| Date Published: | 2009-08-01 |
| Start Page: | 2662 |
| End Page: | 2672 |
| Language: | English |
| DOI: | 10.1096/fj.08-126920 |
| PUBMED: | 19325038 |
| PROVIDER: | scopus |
| PMCID: | PMC2717767 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 30 November 2010" - "CODEN: FAJOE" - "Source: Scopus" |
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