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Article: Characteristics of ABCC4 and ABCG2 High Expression Subpopulations in CRC-A New Opportunity to Predict Therapy Response.

Kryczka, Jakub / Boncela, Joanna

2023 Volume 15, Issue 23

Abstract: Background: Our previous findings proved that ABCC4 and ABCG2 proteins present much more complex roles in colorectal cancer (CRC) than typically cancer-associated functions as drug exporters. Our objective was to evaluate their predictive/diagnostic ... ...

Abstract	Background: Our previous findings proved that ABCC4 and ABCG2 proteins present much more complex roles in colorectal cancer (CRC) than typically cancer-associated functions as drug exporters. Our objective was to evaluate their predictive/diagnostic potential. Methods: CRC patients' transcriptomic data from the Gene Expression Omnibus database (GSE18105, GSE21510 and GSE41568) were discriminated into two subpopulations presenting either high expression levels of ABCC4 (ABCC4 High) or ABCG2 (ABCG2 High). Subpopulations were analysed using various bioinformatical tools and platforms (KEEG, Gene Ontology, FunRich v3.1.3, TIMER2.0 and STRING 12.0). Results: The analysed subpopulations present different gene expression patterns. The protein-protein interaction network of subpopulation-specific genes revealed the top hub proteins in ABCC4 High: RPS27A, SRSF1, DDX3X, BPTF, RBBP7, POLR1B, HNRNPA2B1, PSMD14, NOP58 and EIF2S3 and in ABCG2 High: MAPK3, HIST2H2BE, LMNA, HIST1H2BD, HIST1H2BK, HIST1H2AC, FYN, TLR4, FLNA and HIST1H2AJ. Additionally, our multi-omics analysis proved that the ABCC4 expression correlates with substantially increased tumour-associated macrophage infiltration and sensitivity to FOLFOX treatment. Conclusions: ABCC4 and ABCG2 may be used to distinguish CRC subpopulations that present different molecular and physiological functions. The ABCC4 High subpopulation demonstrates significant EMT reprogramming, RNA metabolism and high response to DNA damage stimuli. The ABCG2 High subpopulation may resist the anti-EGFR therapy, presenting higher proteolytical activity.
Language	English
Publishing date	2023-11-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15235623
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Integrated Bioinformatics Analysis of the Hub Genes Involved in Irinotecan Resistance in Colorectal Cancer.

Kryczka, Jakub / Boncela, Joanna

Biomedicines

2022 Volume 10, Issue 7

Abstract: Different drug combinations including irinotecan remain some of the most important therapeutic modalities in treating colorectal cancer (CRC). However, chemotherapy often leads to the acquisition of cancer drug resistance. To bridge the gap between in ... ...

Abstract	Different drug combinations including irinotecan remain some of the most important therapeutic modalities in treating colorectal cancer (CRC). However, chemotherapy often leads to the acquisition of cancer drug resistance. To bridge the gap between in vitro and in vivo models, we compared the mRNA expression profiles of CRC cell lines (HT29, HTC116, and LoVo and their respective irinotecan-resistant variants) with patient samples to select new candidate genes for the validation of irinotecan resistance. Data were downloaded from the Gene Expression Omnibus (GEO) (GSE42387, GSE62080, and GSE18105) and the Human Protein Atlas databases and were subjected to an integrated bioinformatics analysis. The protein-protein interaction (PPI) network of differently expressed genes (DEGs) between FOLFIRI-resistant and -sensitive CRC patients delivered several potential irinotecan resistance markers: NDUFA2, SDHD, LSM5, DCAF4, COX10 RBM8A, TIMP1, QKI, TGOLN2, and PTGS2. The chosen DEGs were used to validate irinotecan-resistant cell line models, proving their substantial phylogenetic heterogeneity. These results indicated that in vitro models are highly limited and favor different mechanisms than in vivo, patient-derived ones. Thus, cell lines can be perfectly utilized to analyze specific mechanisms on their molecular levels but cannot mirror the complicated drug resistance network observed in patients.
Language	English
Publishing date	2022-07-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10071720
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Article ; Online: Gelatin In Situ Zymography to Study Gelatinase Activity in Colon Cancer Cells Treated with Platelet Microparticles (PMPs).

Kryczka, Jakub / Kassassir, Hassan / Papiewska-Pająk, Izabela / Boncela, Joanna

Methods in molecular biology (Clifton, N.J.)

2023 Volume 2747, Page(s) 167–176

Abstract: The platelet-derived microparticles (PMPs) have been connected with tumor progression and metastatic dissemination. PMPs infiltrate solid tumors and transfer platelet-derived cargo to cancer cells. The functional roles of PMPs in cancer progression are ... ...

Abstract	The platelet-derived microparticles (PMPs) have been connected with tumor progression and metastatic dissemination. PMPs infiltrate solid tumors and transfer platelet-derived cargo to cancer cells. The functional roles of PMPs in cancer progression are still poorly understood. PMPs, incorporated by colorectal cancer (CRC) cells, were shown to upregulate the expression and activity of matrix metalloproteases (MMPs). To investigate the impact of PMPs on the invasive potential of CRC, we established the protocol of dequenched gelatin (DG), fluorescein conjugate assay. The procedure confirms the activity of two gelatinases, namely, MMP2 and MMP9, that digest denatured collagen (gelatin). This "step-by-step" protocol, with notes and comments implemented to human CRC lines with different phenotypes and migratory potentials, should be sufficient to obtain representative and elegant results.
MeSH term(s)	Humans ; Gelatinases/metabolism ; Cell-Derived Microparticles/metabolism ; Gelatin/metabolism ; Blood Platelets/metabolism ; Colonic Neoplasms/metabolism
Chemical Substances	Gelatinases (EC 3.4.24.-) ; Gelatin (9000-70-8)
Language	English
Publishing date	2023-10-31
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3589-6_14
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Article: Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural Mesothelioma.

Chmielewska-Kassassir, Małgorzata / Sobierajska, Katarzyna / Ciszewski, Wojciech M / Kryczka, Jakub / Zieleniak, Andrzej / Wozniak, Lucyna A

Cancers

2023 Volume 15, Issue 20

Abstract: Purpose: To determine the mechanism of EPE in downregulating TYMS in MPM cancer.: Methods: The TYMS mRNA expression with epithelial-to-mesenchymal transition biomarkers and nuclear factor SP1 was assessed using the GEO database in a data set of MPM ... ...

Abstract	Purpose: To determine the mechanism of EPE in downregulating TYMS in MPM cancer. Methods: The TYMS mRNA expression with epithelial-to-mesenchymal transition biomarkers and nuclear factor SP1 was assessed using the GEO database in a data set of MPM patients (GSE51024). Invasive MPM cell lines were in vitro models for the investigation of TYMS expression after EPE treatment. The Results: In MPM patients, a positive correlation of overexpressed TYMS with mesenchymal TWIST1, FN1 and N-cadherin was observed. EPE and its major components, gallic and ellagic acid (GA and EA, respectively), downregulated TYMS in invasive MPM cells by interacting with particular SP1 motifs on the Conclusion: EPE components reduced TYMS expression by occupation of SP1 motifs on the
Language	English
Publishing date	2023-10-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15205003
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Article ; Online: Platelet-derived microparticles stimulate the invasiveness of colorectal cancer cells via the p38MAPK-MMP-2/MMP-9 axis.

Kassassir, Hassan / Papiewska-Pająk, Izabela / Kryczka, Jakub / Boncela, Joanna / Kowalska, M Anna

Cell communication and signaling : CCS

2023 Volume 21, Issue 1, Page(s) 51

Abstract: Background: Metastasis is the main cause of death in patients with colorectal cancer (CRC). Apart from platelets, platelet-derived microparticles (PMPs) are also considered important factors that can modify the activity of cancer cells. PMPs are ... ...

Abstract	Background: Metastasis is the main cause of death in patients with colorectal cancer (CRC). Apart from platelets, platelet-derived microparticles (PMPs) are also considered important factors that can modify the activity of cancer cells. PMPs are incorporated by cancer cells and can also serve as intracellular signalling vesicles. PMPs are believed to affect cancer cells by upregulating their invasiveness. To date, there is no evidence that such a mechanism occurs in colorectal cancer. It has been shown that platelets can stimulate metalloproteases (MMPs) expression and activity via the p38MAPK pathway in CRC cells, leading to their elevated migratory potential. This study aimed to investigate the impact of PMPs on the invasive potential of CRC cells of various phenotypes via the MMP-2, MMP-9 and p38MAPK axis. Methods: We used various CRC cell lines, including the epithelial-like HT29 and the mesenchymal-like SW480 and SW620. Confocal imaging was applied to study PMP incorporation into CRC cells. The presence of surface receptors on CRC cells after PMP uptake was evaluated by flow cytometry. Transwell and scratch wound-healing assays were used to evaluate cell migration. The level of C-X-C chemokine receptor type 4 (CXCR4), MMP-2, and MMP-9 and the phosphorylation of ERK1/2 and p38MAPK were measured by western blot. MMP activity was determined using gelatine-degradation assays, while MMP release was evaluated by ELISA. Results: We found that CRC cells could incorporate PMPs in a time-dependent manner. Moreover, PMPs could transfer platelet-specific integrins and stimulate the expression of integrins already present on tested cell lines. While mesenchymal-like cells expressed less CXCR4 than epithelial-like CRC cells, PMP uptake did not increase its intensity. No significant changes in CXCR4 level either on the surface or inside CRC cells were noticed. Levels of cellular and released MMP-2 and MMP-9 were elevated in all tested CRC cell lines after PMP uptake. PMPs increased the phosphorylation of p38MAPK but not that of ERK1/2. Inhibition of p38MAPK phosphorylation reduced the PMP-induced elevated level and release of MMP-2 and MMP-9 as well as MMP-dependent cell migration in all cell lines. Conclusions: We conclude that PMPs can fuse into both epithelial-like and mesenchymal-like CRC cells and increase their invasive potential by inducing the expression and release of MMP-2 and MMP-9 via the p38MAPK pathway, whereas CXCR4-related cell motility or the ERK1/2 pathway appears to not be affected by PMPs. Video Abstract.
MeSH term(s)	Humans ; Cell-Derived Microparticles ; Colorectal Neoplasms ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; Signal Transduction ; Neoplasm Invasiveness
Chemical Substances	Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
Language	English
Publishing date	2023-03-07
Publishing country	England
Document type	Video-Audio Media ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126315-2
ISSN	1478-811X ; 1478-811X
ISSN (online)	1478-811X
ISSN	1478-811X
DOI	10.1186/s12964-023-01066-8
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Article ; Online: Sentiment analysis of the Twitter response to Netflix's Our Planet documentary

Acerbi, Alberto / Burns, John / Cabuk, Unal / Kryczka, Jakub / Trapp, Bethany / Valletta, John Joseph / Mesoudi, Alex

Conservation Biology. 2023 Aug., v. 37, no. 4 p.e14060-

2023

Abstract: The role of nature documentaries in shaping public attitudes and behavior toward conservation and wildlife issues is unclear. We analyzed the emotional content of over 2 million tweets related to Our Planet, a major nature documentary released on Netflix, ...

Abstract	The role of nature documentaries in shaping public attitudes and behavior toward conservation and wildlife issues is unclear. We analyzed the emotional content of over 2 million tweets related to Our Planet, a major nature documentary released on Netflix, with dictionary and rule‐based automatic sentiment analysis. We also compared the sentiment associated with species mentioned in Our Planet and a set of control species with similar features but not mentioned in the documentary. Tweets were largely negative in sentiment at the time of release of the series. This effect was primarily linked to the highly skewed distributions of retweets and, in particular, to a single negatively valenced and massively retweeted tweet (>150,000 retweets). Species mentioned in Our Planet were associated with more negative sentiment than the control species, and this effect coincided with a short period following the airing of the series. Our results are consistent with a general negativity bias in cultural transmission and document the difficulty of evoking positive sentiment, on social media and elsewhere, in response to environmental problems.
Keywords	air ; public opinion ; social networks ; time series analysis ; wildlife management
Language	English
Dates of publication	2023-08
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	58735-7
ISSN	1523-1739 ; 0888-8892
ISSN (online)	1523-1739
ISSN	0888-8892
DOI	10.1111/cobi.14060
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Cell Migration Related to MDR-Another Impediment to Effective Chemotherapy?

Kryczka, Jakub / Boncela, Joanna

Molecules (Basel, Switzerland)

2018 Volume 23, Issue 2

Abstract: Multidrug resistance, mediated by members of the ATP-binding cassette (ABC) proteins superfamily, has become one of the biggest obstacles in conquering tumour progression. If the chemotherapy outcome is considered successful, when the primary tumour ... ...

Abstract	Multidrug resistance, mediated by members of the ATP-binding cassette (ABC) proteins superfamily, has become one of the biggest obstacles in conquering tumour progression. If the chemotherapy outcome is considered successful, when the primary tumour volume is decreased or completely abolished, modulation of ABC proteins activity is one of the best methods to overcome drug resistance. However, if a positive outcome is represented by no metastasis or, at least, elongation of remission-free time, then the positive effect of ABC proteins inhibition should be compared with the several side effects it causes, which may inflict cancer progression and decrease overall patient health. Clinical trials conducted thus far have shown that the tested ABC modulators add limited or no benefits to cancer patients, as some of them are merely toxic and others induce unwanted drug-drug interactions. Moreover, the inhibition of certain ABC members has been recently indicated as potentially responsible for increased fibroblasts migration. A better understanding of the complex role of ABC proteins in relation to cancer progression may offer novel strategies in cancer therapy.
MeSH term(s)	ATP-Binding Cassette Transporters/antagonists & inhibitors ; ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/metabolism ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/adverse effects ; Antineoplastic Agents/pharmacology ; Cancer-Associated Fibroblasts/drug effects ; Cancer-Associated Fibroblasts/metabolism ; Cancer-Associated Fibroblasts/pathology ; Cell Movement/drug effects ; Cyclosporine/administration & dosage ; Cyclosporine/adverse effects ; Disease Progression ; Drug Resistance, Multiple/genetics ; Drug Resistance, Neoplasm/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Treatment Failure ; Verapamil/administration & dosage ; Verapamil/adverse effects
Chemical Substances	ATP-Binding Cassette Transporters ; Antibodies, Monoclonal ; Antineoplastic Agents ; Neoplasm Proteins ; Cyclosporine (83HN0GTJ6D) ; Verapamil (CJ0O37KU29)
Language	English
Publishing date	2018-02-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules23020331
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Article ; Online: Proteases Revisited: Roles and Therapeutic Implications in Fibrosis.

Kryczka, Jakub / Boncela, Joanna

Mediators of inflammation

2017 Volume 2017, Page(s) 2570154

Abstract: Proteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM ... ...

Abstract	Proteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM degradation, activation of other proteases (i.e., proteolysis of nonactive zymogens), decomposition of cell-cell junctions, release of sequestered growth factors (TGF-
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1137605-3
ISSN	1466-1861 ; 0962-9351
ISSN (online)	1466-1861
ISSN	0962-9351
DOI	10.1155/2017/2570154
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Article ; Online: The Comparison of Serum Exosome Protein Profile in Diagnosis of NSCLC Patients.

Baran, Kamila / Waśko, Joanna / Kryczka, Jakub / Boncela, Joanna / Jabłoński, Sławomir / Kolesińska, Beata / Brzeziańska-Lasota, Ewa / Kordiak, Jacek

International journal of molecular sciences

2023 Volume 24, Issue 18

Abstract: A thorough study of the exosomal proteomic cargo may enable the identification of proteins that play an important role in cancer development. The aim of this study was to compare the protein profiles of the serum exosomes derived from non-small lung ... ...

Abstract	A thorough study of the exosomal proteomic cargo may enable the identification of proteins that play an important role in cancer development. The aim of this study was to compare the protein profiles of the serum exosomes derived from non-small lung cancer (NSCLC) patients and healthy volunteers (control) using the high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS) method to identify potentially new diagnostic and/or prognostic protein biomarkers. Proteins exclusively identified in NSCLC and control groups were analyzed using several bioinformatic tools and platforms (FunRich, Vesiclepedia, STRING, and TIMER2.0) to find key protein hubs involved in NSCLC progression and the acquisition of metastatic potential. This analysis revealed 150 NSCLC proteins, which are significantly involved in osmoregulation, cell-cell adhesion, cell motility, and differentiation. Among them, 3 proteins: Interleukin-34 (IL-34), HLA class II histocompatibility antigen, DM alpha chain (HLA-DMA), and HLA class II histocompatibility antigen, DO beta chain (HLA-DOB) were shown to be significantly involved in the cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) infiltration processes. Additionally, detected proteins were analyzed according to the presence of lymph node metastasis, showing that differences in frequency of detection of protein FAM166B, killer cell immunoglobulin-like receptor 2DL1, and olfactory receptor 52R1 correlate with the N feature according to the TNM Classification of Malignant Tumors. These results prove their involvement in NSCLC lymph node spread and metastasis. However, this study requires further investigation.
MeSH term(s)	Humans ; Exosomes ; Proteomics ; Lung Neoplasms/diagnosis ; Histocompatibility Antigens Class II ; Cancer-Associated Fibroblasts
Chemical Substances	Histocompatibility Antigens Class II
Language	English
Publishing date	2023-09-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241813669
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Article ; Online: Sentiment analysis of the Twitter response to Netflix's Our Planet documentary.

Acerbi, Alberto / Burns, John / Cabuk, Unal / Kryczka, Jakub / Trapp, Bethany / Valletta, John Joseph / Mesoudi, Alex

Conservation biology : the journal of the Society for Conservation Biology

2023 Volume 37, Issue 4, Page(s) e14060

Abstract	The role of nature documentaries in shaping public attitudes and behavior toward conservation and wildlife issues is unclear. We analyzed the emotional content of over 2 million tweets related to Our Planet, a major nature documentary released on Netflix, with dictionary and rule-based automatic sentiment analysis. We also compared the sentiment associated with species mentioned in Our Planet and a set of control species with similar features but not mentioned in the documentary. Tweets were largely negative in sentiment at the time of release of the series. This effect was primarily linked to the highly skewed distributions of retweets and, in particular, to a single negatively valenced and massively retweeted tweet (>150,000 retweets). Species mentioned in Our Planet were associated with more negative sentiment than the control species, and this effect coincided with a short period following the airing of the series. Our results are consistent with a general negativity bias in cultural transmission and document the difficulty of evoking positive sentiment, on social media and elsewhere, in response to environmental problems.
MeSH term(s)	Humans ; Social Media ; Planets ; Sentiment Analysis ; Conservation of Natural Resources ; Attitude
Language	English
Publishing date	2023-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	58735-7
ISSN	1523-1739 ; 0888-8892
ISSN (online)	1523-1739
ISSN	0888-8892
DOI	10.1111/cobi.14060
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