Functional Imaging of Proteolysis: Stromal and Inflammatory Cells Increase Tumor Proteolysis
The underlying basement membrane is degraded during progression of breast and colon carcinoma. Thus, we imaged degradation of a quenched fluorescent derivative of basement membrane type IV collagen (DQ-collagen IV) by living human breast and colon tumor spheroids. Proteolysis of DQ-collagen IV by HC...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi - SAGE Publishing
2003-07-01
|
Series: | Molecular Imaging |
Online Access: | https://doi.org/10.1162/15353500200303136 |
id |
doaj-0fa43bc4d3e644f08b4bc96ec73fb877 |
---|---|
record_format |
Article |
spelling |
doaj-0fa43bc4d3e644f08b4bc96ec73fb8772021-04-02T11:42:09ZengHindawi - SAGE PublishingMolecular Imaging1536-01212003-07-01210.1162/1535350020030313610.1162_15353500200303136Functional Imaging of Proteolysis: Stromal and Inflammatory Cells Increase Tumor ProteolysisMansoureh SameniJulie DosescuKamiar MoinBonnie F. SloaneThe underlying basement membrane is degraded during progression of breast and colon carcinoma. Thus, we imaged degradation of a quenched fluorescent derivative of basement membrane type IV collagen (DQ-collagen IV) by living human breast and colon tumor spheroids. Proteolysis of DQ-collagen IV by HCT 116 and HKh-2 human colon tumor spheroids was both intracellular and pericellular. In contrast, proteolysis of DQ-collagen IV by BT20 human breast tumor spheroids was pericellular. As stromal elements can contribute to proteolytic activities associated with tumors, we also examined degradation of DQ-collagen IV by human monocytes/macrophages and colon and breast fibroblasts. Fibroblasts themselves exhibited a modest amount of pericellular degradation. Degradation was increased 4–17-fold in cocultures of fibroblasts and tumor cells as compared to either cell type alone. Inhibitors of matrix metalloproteinases, plasmin, and the cysteine protease, cathepsin B, all reduced degradation in the cocultures. Monocytes did not degrade DQ-collagen IV; however, macrophages degraded DQ-collagen IV intracellularly. In coculture of tumor cells, fibroblasts, and macrophages, degradation of DQ-collagen IV was further increased. Imaging of living tumor and stromal cells has, thus, allowed us to establish that tumor proteolysis occurs pericellularly and intracellularly and that tumor, stromal, and inflammatory cells all contribute to degradative processes.https://doi.org/10.1162/15353500200303136 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mansoureh Sameni Julie Dosescu Kamiar Moin Bonnie F. Sloane |
spellingShingle |
Mansoureh Sameni Julie Dosescu Kamiar Moin Bonnie F. Sloane Functional Imaging of Proteolysis: Stromal and Inflammatory Cells Increase Tumor Proteolysis Molecular Imaging |
author_facet |
Mansoureh Sameni Julie Dosescu Kamiar Moin Bonnie F. Sloane |
author_sort |
Mansoureh Sameni |
title |
Functional Imaging of Proteolysis: Stromal and Inflammatory Cells Increase Tumor Proteolysis |
title_short |
Functional Imaging of Proteolysis: Stromal and Inflammatory Cells Increase Tumor Proteolysis |
title_full |
Functional Imaging of Proteolysis: Stromal and Inflammatory Cells Increase Tumor Proteolysis |
title_fullStr |
Functional Imaging of Proteolysis: Stromal and Inflammatory Cells Increase Tumor Proteolysis |
title_full_unstemmed |
Functional Imaging of Proteolysis: Stromal and Inflammatory Cells Increase Tumor Proteolysis |
title_sort |
functional imaging of proteolysis: stromal and inflammatory cells increase tumor proteolysis |
publisher |
Hindawi - SAGE Publishing |
series |
Molecular Imaging |
issn |
1536-0121 |
publishDate |
2003-07-01 |
description |
The underlying basement membrane is degraded during progression of breast and colon carcinoma. Thus, we imaged degradation of a quenched fluorescent derivative of basement membrane type IV collagen (DQ-collagen IV) by living human breast and colon tumor spheroids. Proteolysis of DQ-collagen IV by HCT 116 and HKh-2 human colon tumor spheroids was both intracellular and pericellular. In contrast, proteolysis of DQ-collagen IV by BT20 human breast tumor spheroids was pericellular. As stromal elements can contribute to proteolytic activities associated with tumors, we also examined degradation of DQ-collagen IV by human monocytes/macrophages and colon and breast fibroblasts. Fibroblasts themselves exhibited a modest amount of pericellular degradation. Degradation was increased 4–17-fold in cocultures of fibroblasts and tumor cells as compared to either cell type alone. Inhibitors of matrix metalloproteinases, plasmin, and the cysteine protease, cathepsin B, all reduced degradation in the cocultures. Monocytes did not degrade DQ-collagen IV; however, macrophages degraded DQ-collagen IV intracellularly. In coculture of tumor cells, fibroblasts, and macrophages, degradation of DQ-collagen IV was further increased. Imaging of living tumor and stromal cells has, thus, allowed us to establish that tumor proteolysis occurs pericellularly and intracellularly and that tumor, stromal, and inflammatory cells all contribute to degradative processes. |
url |
https://doi.org/10.1162/15353500200303136 |
work_keys_str_mv |
AT mansourehsameni functionalimagingofproteolysisstromalandinflammatorycellsincreasetumorproteolysis AT juliedosescu functionalimagingofproteolysisstromalandinflammatorycellsincreasetumorproteolysis AT kamiarmoin functionalimagingofproteolysisstromalandinflammatorycellsincreasetumorproteolysis AT bonniefsloane functionalimagingofproteolysisstromalandinflammatorycellsincreasetumorproteolysis |
_version_ |
1721571532368510976 |