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Cathepsin L secretion by host and neoplastic cells potentiates invasion
The presence of macrophages within breast tumors correlates with metastatic potential. These tumor-associated macrophages often take on a pro-tumorigenic (M2-like) phenotype resulting in the secretion of growth factors and proteases, including the lysosomal protease cathepsin L. Since cathepsin L al...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756864/ https://www.ncbi.nlm.nih.gov/pubmed/31565189 http://dx.doi.org/10.18632/oncotarget.27182 |
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author | Dykes, Samantha S. Fasanya, Henrietta O. Siemann, Dietmar W. |
author_facet | Dykes, Samantha S. Fasanya, Henrietta O. Siemann, Dietmar W. |
author_sort | Dykes, Samantha S. |
collection | PubMed |
description | The presence of macrophages within breast tumors correlates with metastatic potential. These tumor-associated macrophages often take on a pro-tumorigenic (M2-like) phenotype resulting in the secretion of growth factors and proteases, including the lysosomal protease cathepsin L. Since cathepsin L also is frequently secreted by breast cancer cells and contributes to tumor invasion, metastasis, and angiogenesis, we hypothesized that secretion of cathepsin L by both tumor-associated macrophages and neoplastic cells would facilitate the metastatic phenotype. Our results showed that the novel cathepsin L/K inhibitors KGP94 and KGP207 could inhibit in vitro M2 macrophage invasion and reduce the macrophage-stimulated invasion of 4T1 murine breast cancer cells. KGP94 and KGP207 treatment also reduced the expression of several M2-associated markers, suggesting that cathepsin L activity may be important for IL-4-driven M0 to M2 differentiation. In addition, cathepsin L shRNA knockdown studies revealed that cathepsin L from both the tumor cell and the macrophage population is important for tumor cell invasion. Thus our data suggest that tumor cells and macrophages may both contribute to the cathepsin L-driven metastatic phenotype of breast cancer. Taken together, these studies highlight the importance of cathepsin L in macrophage functions and suggest that cathepsin inhibition strategies may be therapeutically beneficial by impairing the progression of tumors with high infiltration of M2 macrophages. |
format | Online Article Text |
id | pubmed-6756864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-67568642019-09-27 Cathepsin L secretion by host and neoplastic cells potentiates invasion Dykes, Samantha S. Fasanya, Henrietta O. Siemann, Dietmar W. Oncotarget Research Paper The presence of macrophages within breast tumors correlates with metastatic potential. These tumor-associated macrophages often take on a pro-tumorigenic (M2-like) phenotype resulting in the secretion of growth factors and proteases, including the lysosomal protease cathepsin L. Since cathepsin L also is frequently secreted by breast cancer cells and contributes to tumor invasion, metastasis, and angiogenesis, we hypothesized that secretion of cathepsin L by both tumor-associated macrophages and neoplastic cells would facilitate the metastatic phenotype. Our results showed that the novel cathepsin L/K inhibitors KGP94 and KGP207 could inhibit in vitro M2 macrophage invasion and reduce the macrophage-stimulated invasion of 4T1 murine breast cancer cells. KGP94 and KGP207 treatment also reduced the expression of several M2-associated markers, suggesting that cathepsin L activity may be important for IL-4-driven M0 to M2 differentiation. In addition, cathepsin L shRNA knockdown studies revealed that cathepsin L from both the tumor cell and the macrophage population is important for tumor cell invasion. Thus our data suggest that tumor cells and macrophages may both contribute to the cathepsin L-driven metastatic phenotype of breast cancer. Taken together, these studies highlight the importance of cathepsin L in macrophage functions and suggest that cathepsin inhibition strategies may be therapeutically beneficial by impairing the progression of tumors with high infiltration of M2 macrophages. Impact Journals LLC 2019-09-17 /pmc/articles/PMC6756864/ /pubmed/31565189 http://dx.doi.org/10.18632/oncotarget.27182 Text en Copyright: © 2019 Dykes et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Dykes, Samantha S. Fasanya, Henrietta O. Siemann, Dietmar W. Cathepsin L secretion by host and neoplastic cells potentiates invasion |
title | Cathepsin L secretion by host and neoplastic cells potentiates invasion |
title_full | Cathepsin L secretion by host and neoplastic cells potentiates invasion |
title_fullStr | Cathepsin L secretion by host and neoplastic cells potentiates invasion |
title_full_unstemmed | Cathepsin L secretion by host and neoplastic cells potentiates invasion |
title_short | Cathepsin L secretion by host and neoplastic cells potentiates invasion |
title_sort | cathepsin l secretion by host and neoplastic cells potentiates invasion |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756864/ https://www.ncbi.nlm.nih.gov/pubmed/31565189 http://dx.doi.org/10.18632/oncotarget.27182 |
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