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Article ; Online: Human galectin‑3: Molecular switch of gene expression in dermal fibroblasts in vitro and of skin collagen organization in open wounds and tensile strength in incisions

Gál, Peter / Vasilenko, Tomáš / Kováč, Ivan / Čoma, Matúš / Jakubčo, Ján / Jakubčová, Martina / Peržeľová, Vlasta / Urban, Lukáš / Kolář, Michal / Sabol, František / Luczy, Ján / Novotný, Martin / Majerník, Jaroslav / Gabius, Hans-Joachim / Smetana, Karel Jr

Molecular medicine reports

2020 Volume 23, Issue 2

Abstract: Understanding the molecular and cellular processes in skin wound healing can pave the way for devising innovative concepts by turning the identified natural effectors into therapeutic tools. Based on the concept of broad‑scale engagement of members of ... ...

Abstract	Understanding the molecular and cellular processes in skin wound healing can pave the way for devising innovative concepts by turning the identified natural effectors into therapeutic tools. Based on the concept of broad‑scale engagement of members of the family of galactoside‑binding lectins (galectins) in pathophysiological processes, such as cancer or tissue repair/regeneration, the present study investigated the potential of galectins‑1 (Gal‑1) and ‑3 (Gal‑3) in wound healing. Human dermal fibroblasts, which are key cells involved in skin wound healing, responded to galectin exposure (Gal‑1 at 300 or Gal‑3 at 600 ng/ml) with selective changes in gene expression among a panel of 84 wound‑healing‑related genes, as well as remodeling of the extracellular matrix. In the case of Gal‑3, positive expression of Ki67 and cell number increased when using a decellularized matrix produced by Gal‑3‑treated fibroblasts as substrate for culture of interfollicular keratinocytes.
MeSH term(s)	Blood Proteins/biosynthesis ; Collagen/biosynthesis ; Dermis/metabolism ; Dermis/pathology ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Galectins/biosynthesis ; Gene Expression Regulation ; Humans ; Tensile Strength ; Wounds and Injuries/metabolism ; Wounds and Injuries/pathology
Chemical Substances	Blood Proteins ; Galectins ; LGALS3 protein, human ; Collagen (9007-34-5)
Language	English
Publishing date	2020-12-10
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2469505-1
ISSN	1791-3004 ; 1791-2997
ISSN (online)	1791-3004
ISSN	1791-2997
DOI	10.3892/mmr.2020.11738
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cancer Microenvironment

Lukas Lacina / Jan Plzak / Ondrej Kodet / Pavol Szabo / Martin Chovanec / Barbora Dvorankova / Karel Smetana Jr.

International Journal of Molecular Sciences, Vol 16, Iss 10, Pp 24094-

What Can We Learn from the Stem Cell Niche

2015 Volume 24110

Abstract: Epidermal stem cells (ESCs) are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle—also ... ...

Abstract	Epidermal stem cells (ESCs) are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle—also known as the bulge region. ECS are also found between basal cells of the interfollicular epidermis or mucous membranes. The non-epithelial elements such as mesenchymal stem cell-like elements of dermis or surrounding adipose tissue can also contribute to this niche formation. Cancer stem cells (CSCs) participate in formation of common epithelial malignant diseases such as basal cell or squamous cell carcinoma. In this review article, we focus on the role of cancer microenvironment with emphasis on the effect of cancer-associated fibroblasts (CAFs). This model reflects various biological aspects of interaction between cancer cell and CAFs with multiple parallels to interaction of normal epidermal stem cells and their niche. The complexity of intercellular interactions within tumor stroma is depicted on example of malignant melanoma, where keratinocytes also contribute the microenvironmental landscape during early phase of tumor progression. Interactions seen in normal bulge region can therefore be an important source of information for proper understanding to melanoma. The therapeutic consequences of targeting of microenvironment in anticancer therapy and for improved wound healing are included to article.
Keywords	stem cell ; niche ; wound healing ; cancer microenvironment ; cancer-associated fibroblast ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2015-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Cyclic chalcone analogue KRP6 as a potent modulator of cell proliferation: an in vitro study in HUVECs

Ivanova, Lenka / Varinska, Lenka / Pilatova, Martina / Gal, Peter / Solar, Peter / Perjesi, Pal / Smetana, Karel, Jr / Ostro, Alexander / Mojzis, Jan

Molecular biology reports. 2013 July, v. 40, no. 7

2013

Abstract: In the present investigation a novel series of chalcone analogues were synthesized and evaluated for their anti-proliferative activity in human umbilical vein endothelial cells (HUVECs). Among 14 tested compounds, chalcone analogue (E)-3-(2′- ... ...

Abstract	In the present investigation a novel series of chalcone analogues were synthesized and evaluated for their anti-proliferative activity in human umbilical vein endothelial cells (HUVECs). Among 14 tested compounds, chalcone analogue (E)-3-(2′-methoxybenzylidene)-4-chromanone (KRP6) exhibited the most potent activity with IC₅₀19 μM. Moreover, HUVECs exhibited divergent, even opposing concentration-dependent responses to KRP6. This compound was the most potent inhibitor of cell proliferation and extracellular matrix formation (fibronectin and type IV collagen) at higher concentrations (20–50 μM). In contrast, KRP6 stimulated the compensatory increase in proliferative activity including extracellular matrix formation at low concentrations (1, 10 μM). KRP6 concentration-dependently modulated phosphorylation of Akt and mitogen-activated protein kinases such as extracellular signal-regulated kinase-1/-2 and p38 kinase, suggesting that these pathways play a role in the effect mediated by this compound. In addition, we found a selective effect on activated endothelial cells, in particular with resting endothelial cells. In conclusion, KRP6 is a potent modulator of selected steps of the angiogenic process in vitro. Accordingly, further in vivo research should be performed to facilitate its use in clinical practice.
Keywords	cell proliferation ; chalcone ; collagen ; extracellular matrix ; fibronectins ; human umbilical vein endothelial cells ; in vitro studies ; mitogen-activated protein kinase ; phosphorylation
Language	English
Dates of publication	2013-07
Size	p. 4571-4580.
Publishing place	Springer-Verlag
Document type	Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-013-2547-x
Database	NAL-Catalogue (AGRICOLA)

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Article: Intercellular crosstalk in human malignant melanoma

DvoÅÃ¡nkovÃ¡, Barbora / Pavol Szabo / OndÅej Kodet / Hynek Strnad / Michal KolÃ¡Å / LukÃ¡Å¡ Lacina / EliÅ¡ka KrejÄÃ / OndÅej NaÅka / Aleksi Å edo / Karel Smetana Jr

Protoplasma. 2017 May, v. 254, no. 3

2017

Abstract: Incidence of malignant melanoma is increasing globally. While the initial stages of tumors can be easily treated by a simple surgery, the therapy of advanced stages is rather limited. Melanoma cells spread rapidly through the body of a patient to form ... ...

Abstract	Incidence of malignant melanoma is increasing globally. While the initial stages of tumors can be easily treated by a simple surgery, the therapy of advanced stages is rather limited. Melanoma cells spread rapidly through the body of a patient to form multiple metastases. Consequently, the survival rate is poor. Therefore, emphasis in melanoma research is given on early diagnosis and development of novel and more potent therapeutic options. The malignant melanoma is arising from melanocytes, cells protecting mitotically active keratinocytes against damage caused by UV light irradiation. The melanocytes originate in the neural crest and consequently migrate to the epidermis. The relationship between the melanoma cells, the melanocytes, and neural crest stem cells manifests when the melanoma cells are implanted to an early embryo: they use similar migratory routes as the normal neural crest cells. Moreover, malignant potential of these melanoma cells is overdriven in this experimental model, probably due to microenvironmental reprogramming. This observation demonstrates the crucial role of the microenvironment in melanoma biology. Indeed, malignant tumors in general represent complex ecosystems, where multiple cell types influence the growth of genetically mutated cancer cells. This concept is directly applicable to the malignant melanoma. Our review article focuses on possible strategies to modify the intercellular crosstalk in melanoma that can be employed for therapeutic purposes.
Keywords	early diagnosis ; ecosystems ; humans ; irradiation ; keratinocytes ; melanocytes ; melanoma ; metastasis ; migratory behavior ; mitosis ; models ; neoplasm cells ; neural crest ; patients ; stem cells ; surgery ; survival rate ; ultraviolet radiation
Language	English
Dates of publication	2017-05
Size	p. 1143-1150.
Publishing place	Springer Vienna
Document type	Article
Note	Review
ZDB-ID	123809-7
ISSN	1615-6102 ; 0033-183X
ISSN (online)	1615-6102
ISSN	0033-183X
DOI	10.1007/s00709-016-1038-z
Database	NAL-Catalogue (AGRICOLA)

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Conference proceedings: Oral squamous cell carcinoma derived stromal cells influence phenotypic characteristics of keratinocytes

Chovanec, Martin / Smetana, Karel Jr. / Lacina, Lukas / Dvorankova, Barbora / Cada, Zdenek / Plzak, Jan / Betka, Jan / Gabius, Hans-Joachim / Andre, Sabine

2008 , Page(s) 08hnod162

Event/congress	79. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; Bonn; Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 2008
Keywords	Medizin, Gesundheit
Publishing date	2008-04-22
Publisher	German Medical Science GMS Publishing House; Düsseldorf
Document type	Conference proceedings
Database	German Medical Science

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Article: Interaction of cells with polymers

Smetana, Karel Jr / Vacík, Jiří / Dvořánková, Barbora

Macromolecular symposia. 1996 May, v. 109, no. 1

1996

Abstract: This paper summarizes the results of our experiments studying the effect of functional chemical groups of synthetic hydrophilic polymers on the recognition of these materials by macrophages in in vivo experiments. The interaction of keratinocytes with ... ...

Abstract	This paper summarizes the results of our experiments studying the effect of functional chemical groups of synthetic hydrophilic polymers on the recognition of these materials by macrophages in in vivo experiments. The interaction of keratinocytes with synthetic hydrophilic polymers in vitro is also demonstrated. The implants containing anionic groups (carboxylates) were shown to be better tolerated by nonspecific immunity. The keratinocytes are able to grow on hydrophilic polymer supports and migrate to surfaces with improved adhesivity (in vitro). The clinical applications of these experiments are demonstrated.
Language	English
Dates of publication	1996-05
Size	p. 145-153.
Publishing place	Hüthig & Wepf Verlag
Document type	Article
ISSN	1022-1360
DOI	10.1002/masy.19961090114
Database	NAL-Catalogue (AGRICOLA)

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Article: Glycobiology of Head and Neck Squamous Epithelia and Carcinomas

Plzák, Jan / Smetana Jr., Karel / Chovanec, Martin / Betka, Jan

ORL

2005 Volume 67, Issue 2, Page(s) 61–69

Abstract: An impressive variety of regulatory processes including cell adhesion and migration, proliferation, apoptosis and differentiation folding and routing of glycoproteins have been found to be mediated by specific lectin-carbohydrate interactions. This ... ...

Institution	Department of Otorhinolaryngology and Head and Neck Surgery and Institute of Anatomy, 1st Faculty of Medicine, and Center of Cell Therapy and Tissue Repair, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
Abstract	An impressive variety of regulatory processes including cell adhesion and migration, proliferation, apoptosis and differentiation folding and routing of glycoproteins have been found to be mediated by specific lectin-carbohydrate interactions. This article summarizes the data on glycobiological aspects of differentiation of squamous epithelia in the head and neck region under physiological conditions and in cancer. The possible function of lectins in tumor development and invasiveness is debated. Introduction of labeled endogenous lectins as a tool for the study of functional glycomics at the cellular level in head and neck squamous epithelia and carcinomas enables a complex interpretation of studied data because these lectins are normally occurring in these tissues. The lectinology of Langerhans cells in head and neck squamous epithelia and carcinoma is also mentioned. Finally, the use of the described data in the diagnosis and prospectively in the treatment of head and neck squamous cell carcinoma is shown.
Keywords	Squamous epithelium ; Head and neck squamous cell carcinoma ; Lectin-carbohydrate interactions
Language	English
Publishing date	2005-05-20
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Review
ZDB-ID	121482-2
ISSN	1423-0275 ; 0301-1569
ISSN (online)	1423-0275
ISSN	0301-1569
DOI	10.1159/000084994
Database	Karger publisher's database

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Article: Head and neck squamous cancer stromal fibroblasts produce growth factors influencing phenotype of normal human keratinocytes

Strnad, Hynek / Lacina, Lukáš / Kolář, Michal / Čada, Zdeněk / Vlček, Čestmír / Dvořánková, Barbora / Betka, Jan / Plzák, Jan / Chovanec, Martin / Šáchová, Jana / Valach, Jaroslav / Urbanová, Markéta / Smetana, Karel Jr

Histochemistry and cell biology. 2010 Feb., v. 133, no. 2

2010

Abstract: Epithelial-mesenchymal interaction between stromal fibroblasts and cancer cells influences the functional properties of tumor epithelium, including the tumor progression and spread. We compared fibroblasts prepared from stroma of squamous cell carcinoma ... ...

Abstract	Epithelial-mesenchymal interaction between stromal fibroblasts and cancer cells influences the functional properties of tumor epithelium, including the tumor progression and spread. We compared fibroblasts prepared from stroma of squamous cell carcinoma and normal dermal fibroblasts concerning their biological activity toward normal keratinocytes assessed by immunocytochemistry and profiling of gene activation for growth factors/cytokines by microarray chip technology. IGF-2 and BMP-4 were determined as candidate factors responsible for tumor-associated fibroblast activity that influences normal epithelia. This effect was confirmed by addition of recombinant IGF-2 and BMP4, respectively, to the culture medium. This hypothesis was also verified by inhibition experiments where blocking antibodies were employed in the medium conditioned by cancer-associated fibroblast. Presence of these growth factors was also detected in tumor samples.
Language	English
Dates of publication	2010-02
Size	p. 201-211.
Publisher	Springer-Verlag
Publishing place	Berlin/Heidelberg
Document type	Article
ZDB-ID	1222930-1
ISSN	1432-119X ; 0301-5564 ; 0948-6143
ISSN (online)	1432-119X
ISSN	0301-5564 ; 0948-6143
DOI	10.1007/s00418-009-0661-6
Database	NAL-Catalogue (AGRICOLA)

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Article: Human Galectins Induce Conversion of Dermal Fibroblasts into Myofibroblasts and Production of Extracellular Matrix: Potential Application in Tissue Engineering and Wound Repair

Dvořánková, Barbora / Szabo, Pavol / Lacina, Lukas / Gal, Peter / Uhrova, Jana / Zima, Tomas / Kaltner, Herbert / André, Sabine / Gabius, Hans-Joachim / Sykova, Eva / Smetana, Jr., Karel

Cells Tissues Organs

2011 Volume 194, Issue 6, Page(s) 469–480

Abstract: Members of the galectin family of endogenous lectins are potent adhesion/growth-regulatory effectors. Their multifunctionality opens possibilities for their use in bioapplications. We studied whether human galectins induce the conversion of human dermal ... ...

Institution	Institute of Anatomy Department of Dermatovenerology Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine Center of Cell Therapy and Tissue Repair, 2nd Faculty of Medicine, Charles University, and Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic Department for Biomedical Research, East-Slovak Institute of Cardiovascular Diseases Department of Pathological Anatomy, University of Veterinary Medicine and Pharmacy, Košice, Slovak Republic Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Munich, Germany
Abstract	Members of the galectin family of endogenous lectins are potent adhesion/growth-regulatory effectors. Their multifunctionality opens possibilities for their use in bioapplications. We studied whether human galectins induce the conversion of human dermal fibroblasts into myofibroblasts (MFBs) and the production of a bioactive extracellular matrix scaffold is suitable for cell culture. Testing a panel of galectins of all three subgroups, including natural and engineered variants, we detected activity for the proto-type galectin-1 and galectin-7, the chimera-type galectin-3 and the tandem-repeat-type galectin-4. The activity of galectin-1 required the integrity of the carbohydrate recognition domain. It was independent of the presence of TGF-β1, but it yielded an additive effect. The resulting MFBs, relevant, for example, for tumor progression, generated a matrix scaffold rich in fibronectin and galectin-1 that supported keratinocyte culture without feeder cells. Of note, keratinocytes cultured on this substratum presented a stem-like cell phenotype with small size and keratin-19 expression. In vivo in rats, galectin-1 had a positive effect on skin wound closure 21 days after surgery. In conclusion, we describe the differential potential of certain human galectins to induce the conversion of dermal fibroblasts into MFBs and the generation of a bioactive cell culture substratum.
Keywords	Extracellular matrix ; Fibronectin ; Keratinocyte ; Lectin ; Tissue engineering
Language	English
Publishing date	2011-04-14
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Original Paper
ZDB-ID	1468141-9
ISSN	1422-6421 ; 1422-6405
ISSN (online)	1422-6421
ISSN	1422-6405
DOI	10.1159/000324864
Database	Karger publisher's database

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Article: Differentiation-Dependent Glycosylation of Cells in Squamous Cell Epithelia Detected by a Mammalian Lectin

Plzák, Jan / Holíková, Zuzana / Smetana Jr., Karel / Dvořánková, Barbora / Hercogová, Jana / Kaltner, Herbert / Motlík, Jan / Gabius, Hans-Joachim

Cells Tissues Organs

2002 Volume 171, Issue 2-3, Page(s) 135–144

Abstract: The squamous stratified epithelia contain a proliferative (harboring mitotic activity) and a differentiating compartment. Due to the potential of protein-carbohydrate interactions to regulate cellular activities we introduced a mammalian lectin to cyto- ... ...

Institution	Institute of Anatomy, 1st Faculty of Medicine Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine Center for Cell Therapy and Tissue Repair, 2nd Faculty of Medicine Department of Dermatology, 2nd Faculty of Medicine, and Department of Burn Surgery, 3rd Faculty of Medicine, Charles University, Prague, and Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Liběchov, Czech Republic Faculty of Veterinary Medicine, Institute of Physiological Chemistry, Ludwig Maximilians University, Munich, Germany
Abstract	The squamous stratified epithelia contain a proliferative (harboring mitotic activity) and a differentiating compartment. Due to the potential of protein-carbohydrate interactions to regulate cellular activities we introduced a mammalian lectin to cyto- and histochemical analysis. We answer the questions of whether and to what extent this new probe can pinpoint differentiation-dependent glycosylation changes in sections and in culture of keratinocytes. Material and Methods: Purification and labeling enabled monitoring of galectin-3 reactivity in frozen sections of human and pig epidermis and basal cell carcinomas as well as in culture of keratinocytes. The staining pattern of the lectin was correlated with the staining profile of other cell markers including desmosomal proteins, β1 integrin, and the proliferation marker Ki-67. The Dolichos biflorus agglutinin (DBA) sharing binding reactivity of galectin-3 to the A type histoblood group epitope was used for comparison. Results: Both lectins exhibit suprabasal binding. However, their profiles were not identical, substantiated by lack of coinhibition. Strong DBA reactivity was also observed in a limited number of basal layer cells, namely in cells without the expression of the proliferation marker Ki-67. Cultured mitotic epidermal cells have no reactivity for DBA. Presence of ligands for this plant lectin was connected with decreased positivity of nuclei for Ki-67 and the occurrence of ring-shaped nucleoli, micronucleoli or absence of nucleoli. Considering colocalization the pattern of galectin-3-binding sites coincided with the presence of desmosomal proteins such as desmoplakin-1 and desmoglein but not β1 integrin, a potential ligand. Interestingly, studied basal cell carcinomas expressed no binding sites for galectin-3, while a limited number of cells were DBA-reactive. Conclusion: The expression of galectin-3-binding sites and also DBA-reactive glycoligands correlates with an increased level of differentiation and/or cessation of proliferation in the examined squamous stratified epithelia. Further application of tissue lectins for characterizing ligand expression and its modulation is an important step to reveal functional relevance.
Keywords	Cell differentiation ; Squamous epithelia ; Galectin-3 ; Lectin ; Carcinoma, basal cell
Language	English
Publishing date	2002-06-28
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Original Paper
ZDB-ID	1468141-9
ISSN	1422-6421 ; 1422-6405
ISSN (online)	1422-6421
ISSN	1422-6405
DOI	10.1159/000063707
Database	Karger publisher's database

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