2018
Kahounová, Zuzana; Kurfürstová, Daniela; Bouchal, Jan; Kharaishvili, Gvantsa; Navrátil, Jiří; Remšík, Ján; Šimečková, Šárka; Študent, Vladimír; Kozubík, Alois; Souček, Karel
In: Cytometry. Part A : the journal of the International Society for Analytical Cytology, vol. 93, no. 9, pp. 941–951, 2018, ISSN: 1552-4930 1552-4922, (Place: United States).
Abstract | Links | BibTeX | Tags: anti-fibroblast, Biomarkers/*metabolism, Breast Neoplasms/metabolism, cancer-associated fibroblasts, Cell Line, Endopeptidases, Epithelial Cell Adhesion Molecule/metabolism, Epithelial Cells/metabolism, Epithelial-Mesenchymal Transition/*physiology, epithelial-to-mesenchymal transition, Female, fibroblast activation protein α, fibroblast surface protein, Fibroblasts/*metabolism, Gelatinases/*metabolism, Humans, Leukocyte Common Antigens/metabolism, Male, Membrane Proteins/*metabolism, PC-3 Cells, Platelet Endothelial Cell Adhesion Molecule-1/metabolism, Prostatic Neoplasms/metabolism, Serine Endopeptidases/*metabolism, Transforming Growth Factor beta1/metabolism, Tumor
@article{kahounova_fibroblast_2018,
title = {The fibroblast surface markers FAP, anti-fibroblast, and FSP are expressed by cells of epithelial origin and may be altered during epithelial-to-mesenchymal transition.},
author = {Zuzana Kahounová and Daniela Kurfürstová and Jan Bouchal and Gvantsa Kharaishvili and Jiří Navrátil and Ján Remšík and Šárka Šimečková and Vladimír Študent and Alois Kozubík and Karel Souček},
doi = {10.1002/cyto.a.23101},
issn = {1552-4930 1552-4922},
year = {2018},
date = {2018-07-01},
journal = {Cytometry. Part A : the journal of the International Society for Analytical Cytology},
volume = {93},
number = {9},
pages = {941–951},
abstract = {The identification of fibroblasts and cancer-associated fibroblasts from human cancer tissue using surface markers is difficult, especially because the markers used currently are usually not expressed solely by fibroblasts, and the identification of fibroblast-specific surface molecules is still under investigation. It was aimed to compare three commercially available antibodies in the detection of different surface epitopes of fibroblasts (anti-fibroblast, fibroblast activation protein α, and fibroblast surface protein). The specificity of their expression, employing fibroblast cell lines and tumor-derived fibroblasts from breast and prostate tissues was investigated. Both the established fibroblast cell line HFF-1 and ex vivo primary fibroblasts isolated from breast and prostate cancer tissues expressed the tested surface markers to different degrees. Surprisingly, those markers were expressed also by permanent cell lines of epithelial origin, both benign and cancer-derived (breast-cell lines MCF 10A, HMLE and prostate-cell lines BPH-1, DU 145, and PC-3). The expression of fibroblast activation protein α increased on the surface of previously described models of epithelial cells undergoing epithelial-to-mesenchymal transition in response to treatment with TGF-β1. To prove the co-expression of the fibroblast markers on cells of epithelial origin, we used freshly dissociated human prostate and breast cancer tissues. The results confirmed the co-expression of anti-fibroblast and fibroblast surface protein on CD31/CD45-negative/EpCAM-positive epithelial cells. In summary, our data support the findings that the tested fibroblast markers are not fibroblast specific and may be expressed also by cells of epithelial origin (e.g., cells undergoing EMT). Therefore, the expression of these markers should be interpreted with caution, and the combination of several epitopes for both positive (anti-fibroblast or fibroblast activation protein α) and negative (EpCAM) identification of fibroblasts from breast and prostate tumor tissues is advised. © 2017 International Society for Advancement of Cytometry.},
note = {Place: United States},
keywords = {anti-fibroblast, Biomarkers/*metabolism, Breast Neoplasms/metabolism, cancer-associated fibroblasts, Cell Line, Endopeptidases, Epithelial Cell Adhesion Molecule/metabolism, Epithelial Cells/metabolism, Epithelial-Mesenchymal Transition/*physiology, epithelial-to-mesenchymal transition, Female, fibroblast activation protein α, fibroblast surface protein, Fibroblasts/*metabolism, Gelatinases/*metabolism, Humans, Leukocyte Common Antigens/metabolism, Male, Membrane Proteins/*metabolism, PC-3 Cells, Platelet Endothelial Cell Adhesion Molecule-1/metabolism, Prostatic Neoplasms/metabolism, Serine Endopeptidases/*metabolism, Transforming Growth Factor beta1/metabolism, Tumor},
pubstate = {published},
tppubtype = {article}
}
The identification of fibroblasts and cancer-associated fibroblasts from human cancer tissue using surface markers is difficult, especially because the markers used currently are usually not expressed solely by fibroblasts, and the identification of fibroblast-specific surface molecules is still under investigation. It was aimed to compare three commercially available antibodies in the detection of different surface epitopes of fibroblasts (anti-fibroblast, fibroblast activation protein α, and fibroblast surface protein). The specificity of their expression, employing fibroblast cell lines and tumor-derived fibroblasts from breast and prostate tissues was investigated. Both the established fibroblast cell line HFF-1 and ex vivo primary fibroblasts isolated from breast and prostate cancer tissues expressed the tested surface markers to different degrees. Surprisingly, those markers were expressed also by permanent cell lines of epithelial origin, both benign and cancer-derived (breast-cell lines MCF 10A, HMLE and prostate-cell lines BPH-1, DU 145, and PC-3). The expression of fibroblast activation protein α increased on the surface of previously described models of epithelial cells undergoing epithelial-to-mesenchymal transition in response to treatment with TGF-β1. To prove the co-expression of the fibroblast markers on cells of epithelial origin, we used freshly dissociated human prostate and breast cancer tissues. The results confirmed the co-expression of anti-fibroblast and fibroblast surface protein on CD31/CD45-negative/EpCAM-positive epithelial cells. In summary, our data support the findings that the tested fibroblast markers are not fibroblast specific and may be expressed also by cells of epithelial origin (e.g., cells undergoing EMT). Therefore, the expression of these markers should be interpreted with caution, and the combination of several epitopes for both positive (anti-fibroblast or fibroblast activation protein α) and negative (EpCAM) identification of fibroblasts from breast and prostate tumor tissues is advised. © 2017 International Society for Advancement of Cytometry.
2009
Vanhara, Petr; Lincová, Eva; Kozubík, Alois; Jurdic, Pierre; Soucek, Karel; Smarda, Jan
Growth/differentiation factor-15 inhibits differentiation into osteoclasts–a novel factor involved in control of osteoclast differentiation. Journal Article
In: Differentiation; research in biological diversity, vol. 78, no. 4, pp. 213–222, 2009, ISSN: 1432-0436 0301-4681, (Place: England).
Abstract | Links | BibTeX | Tags: Acid Phosphatase/metabolism, Animals, Calcitriol/pharmacology, Carbonic Anhydrase II/antagonists & inhibitors, Cathepsin K/antagonists & inhibitors/genetics, Cell Differentiation/*drug effects, Cell Line, Conditioned/pharmacology, Culture Media, Dose-Response Relationship, Drug, Femur/cytology, Growth Differentiation Factor 15/*pharmacology, Humans, Inbred Strains, Isoenzymes/metabolism, Macrophage Colony-Stimulating Factor/pharmacology, Macrophages/cytology, Male, Mice, NF-kappa B/antagonists & inhibitors, Osteoclasts/*drug effects/metabolism, Prostatic Neoplasms/metabolism, Proto-Oncogene Proteins c-fos/antagonists & inhibitors, RANK Ligand/pharmacology, Tartrate-Resistant Acid Phosphatase, Time Factors, Tumor
@article{vanhara_growthdifferentiation_2009,
title = {Growth/differentiation factor-15 inhibits differentiation into osteoclasts–a novel factor involved in control of osteoclast differentiation.},
author = {Petr Vanhara and Eva Lincová and Alois Kozubík and Pierre Jurdic and Karel Soucek and Jan Smarda},
doi = {10.1016/j.diff.2009.07.008},
issn = {1432-0436 0301-4681},
year = {2009},
date = {2009-11-01},
journal = {Differentiation; research in biological diversity},
volume = {78},
number = {4},
pages = {213–222},
abstract = {Survival and capability of cancer cells to form metastases fundamentally depend on interactions with their microenvironment. Secondary tumors originating from prostate carcinomas affect remodeling of bone tissue and can induce both osteolytic and osteocondensing lesions. However, particular molecular mechanisms responsible for selective homing and activity of cancer cells in bone microenvironment have not been clarified yet. Growth/differentiation factor-15 (GDF-15), a distant member of the TGF-beta protein family, has recently been associated with many human cancers, including prostate. We show that both pure GDF-15 and the GDF-15-containing growth medium of 1,25(OH)(2)-vitamin D(3)-treated prostate adenocarcinoma LNCaP cells suppress formation of mature osteoclasts differentiated from RAW264.7 macrophages and bone-marrow precursors by M-CSF/RANKL in a dose-dependent manner. GDF-15 inhibits expression of c-Fos and activity of NFkappaB by delayed degradation of IkappaB. Moreover, GDF-15 inhibits expression of carbonic anhydrase II and cathepsin K, key osteoclast enzymes, and induces changes in SMAD and p38 signaling. The lack of functional osteoclasts can contribute to accumulation of bone matrix by reduction of bone resorption. These results unveil new role of GDF-15 in modulation of osteoclast differentiation and possibly in therapy of bone metastases.},
note = {Place: England},
keywords = {Acid Phosphatase/metabolism, Animals, Calcitriol/pharmacology, Carbonic Anhydrase II/antagonists & inhibitors, Cathepsin K/antagonists & inhibitors/genetics, Cell Differentiation/*drug effects, Cell Line, Conditioned/pharmacology, Culture Media, Dose-Response Relationship, Drug, Femur/cytology, Growth Differentiation Factor 15/*pharmacology, Humans, Inbred Strains, Isoenzymes/metabolism, Macrophage Colony-Stimulating Factor/pharmacology, Macrophages/cytology, Male, Mice, NF-kappa B/antagonists & inhibitors, Osteoclasts/*drug effects/metabolism, Prostatic Neoplasms/metabolism, Proto-Oncogene Proteins c-fos/antagonists & inhibitors, RANK Ligand/pharmacology, Tartrate-Resistant Acid Phosphatase, Time Factors, Tumor},
pubstate = {published},
tppubtype = {article}
}
Survival and capability of cancer cells to form metastases fundamentally depend on interactions with their microenvironment. Secondary tumors originating from prostate carcinomas affect remodeling of bone tissue and can induce both osteolytic and osteocondensing lesions. However, particular molecular mechanisms responsible for selective homing and activity of cancer cells in bone microenvironment have not been clarified yet. Growth/differentiation factor-15 (GDF-15), a distant member of the TGF-beta protein family, has recently been associated with many human cancers, including prostate. We show that both pure GDF-15 and the GDF-15-containing growth medium of 1,25(OH)(2)-vitamin D(3)-treated prostate adenocarcinoma LNCaP cells suppress formation of mature osteoclasts differentiated from RAW264.7 macrophages and bone-marrow precursors by M-CSF/RANKL in a dose-dependent manner. GDF-15 inhibits expression of c-Fos and activity of NFkappaB by delayed degradation of IkappaB. Moreover, GDF-15 inhibits expression of carbonic anhydrase II and cathepsin K, key osteoclast enzymes, and induces changes in SMAD and p38 signaling. The lack of functional osteoclasts can contribute to accumulation of bone matrix by reduction of bone resorption. These results unveil new role of GDF-15 in modulation of osteoclast differentiation and possibly in therapy of bone metastases.