Alessandra Valéria de Sousa Faria

University of Helsinki

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Carmen Veríssima Ferreira‐Halder

Universidade Estadual de Campinas (UNICAMP)

Maikel P. Peppelenbosch

Erasmus MC

Gwenny M. Fuhler

Erasmus MC

Sheila Siqueira Andrade

Associação Fundo de Incentivo à Pesquisa

Stefano Piatto Clerici

Universidade Estadual de Campinas (UNICAMP)

Emanuella Maria Barreto Fonseca

Federal Institute of São Paulo

Helon Guimarães Cordeiro

Universidade Estadual de Campinas (UNICAMP)

Patrícia Fernandes de Souza Oliveira

Universidade Estadual de Campinas (UNICAMP)

Pia Siljander

University of Helsinki

Manon C.W. Spaander

Erasmus MC

Cooperative Institutions

Universidade Estadual de Campinas (UNICAMP)

Erasmus MC

Erasmus University Rotterdam

Hospital de Clínicas da Unicamp

University of Delhi

Universidade de São Paulo

Erasmus MC Cancer Institute

Weatherford College

University of Helsinki

Hacettepe University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Platelet-derived extracellular vesicles induced through different activation pathways drive melanoma progression by functional and transcriptional changes

Cell Communication and Signaling (2024)

Zeynep Tavukcuoglu Umar Butt Alessandra Valéria de Sousa Faria Johannes Oesterreicher Wolfgang Holnthoner

Abstract Background Beyond their conventional roles in hemostasis and wound healing, platelets have been shown to facilitate hematogenous metastasis by interacting with cancer cells. Depending on the activation route, platelets also generate different platelet-derived extracellular vesicles (PEVs) that may educate cancer cells in the circulation or within the tumor microenvironment. We engaged different platelet-activating receptors, including glycoprotein VI and C-type lectin-like receptor 2, to generate a spectrum of PEV types. This allowed us to investigate the differential capacity of PEVs to alter cancer hallmark functions such as proliferation, invasion, and pro-angiogenic potential using melanoma as a model. Additionally, we analyzed changes in the cell transcriptomes and cancer EV profiles. Methods Two human melanoma cell lines (MV3 and A2058) with differential metastatic potential were studied in the 3D spheroid cultures. Human platelets were activated with collagen related peptide (CRP), fucoidan from Fucus vesiculosus (FFV), thrombin & collagen co-stimulus and Ca 2+ ionophore, and PEVs were isolated by size-exclusion chromatography followed by ultrafiltration. Spheroids or cells were treated with PEVs and used in functional assays of proliferation, invasion, and endothelial tube formation as well as for the analysis of cancer EV production and their tetraspanin profiles. Differentially expressed genes and enriched signaling pathways in the PEV-treated spheroids were analyzed at 6 h and 24 h by RNA sequencing. Results Among the studied PEVs, those generated by CRP and FFV exhibited the most pronounced effects on altering cancer hallmark functions. Specifically, CRP and FFV PEVs increased proliferation in both MV3 and A2058 spheroids. Distinct tetraspanin signatures of melanoma EVs were induced by all PEV types. While the PI3K-Akt and MAPK signaling pathways were activated by both CRP and FFV PEVs, they differently upregulated the immunomodulatory TGF-β and type-I interferon signaling pathways, respectively. Conclusions Our study revealed both shared and distinct, cancer-promoting functions of PEVs, which contributed to the transcriptome and metastatic capabilities of the melanoma spheroids. Inhibiting the platelet receptors that modulate the PEVs’ cancer-promoting properties may open up new strategies for identifying promising treatment targets for cancer therapy.

10.1186/s12964-024-01973-4

Cite

Citations (1)

Extracellular vesicles as a recipe for design smart drug delivery systems for cancer therapy

Elsevier eBooks (2018)

Carmen Veríssima Ferreira Halder Emanuella Maria Barreto Fonseca Alessandra Valéria de Sousa Faria Stefano Piatto Clerici

Extracellular Vesicles

Exosome

Cancer Therapy

Targeted drug delivery

Extracellular vesicles

10.1016/b978-0-12-813689-8.00011-2

Cite

Citations (1)

Correction: Platelet-derived extracellular vesicles induced through different activation pathways drive melanoma progression by functional and transcriptional changes

Cell Communication and Signaling (2025)

Zeynep Tavukcuoglu Umar Butt Alessandra Valéria de Sousa Faria Johannes Oesterreicher Wolfgang Holnthoner

Extracellular Vesicles

10.1186/s12964-024-02026-6

Cite

Citations (0)

Action and function of Faecalibacterium prausnitzii in health and disease

Best Practice & Research Clinical Gastroenterology (2017)

Carmen Veríssima Ferreira‐Halder Alessandra Valéria de Sousa Faria Sheila Siqueira Andrade

Faecalibacterium prausnitzii

Dysbiosis

10.1016/j.bpg.2017.09.011

Cite

Citations (369)

Kinome profiling of cholangiocarcinoma organoids reveals potential druggable targets that hold promise for treatment stratification

Molecular Medicine (2022)

Ruby Lieshout Alessandra Valéria de Sousa Faria Maikel P. Peppelenbosch Luc J. W. van der Laan Monique M.A. Verstegen

Cholangiocarcinoma is a rare but lethal cancer of the biliary tract. Its first-line treatment is currently restricted to chemotherapy, which provides limited clinical benefit. Kinase inhibitors targeting oncogenic intracellular signaling have changed the treatment paradigm of cancer over the last decades. However, they are yet to be widely applied in cholangiocarcinoma therapy. Cholangiocarcinoma has marked molecular heterogeneity, which complicates the discovery of new treatments and requires patient stratification. Therefore, we investigated whether a commercial kinome profiling platform could predict druggable targets in cholangiocarcinoma.Kinase activity in patient-derived cholangiocarcinoma organoids, non-tumorous adjacent tissue-derived and healthy donor-derived intrahepatic cholangiocyte organoids was determined using the PamChip® phosphotyrosine kinase microarray platform. Kinome profiles were compared and correlated with RNA sequencing and (multi-)kinase inhibitor screening of the cholangiocarcinoma organoids.Kinase activity profiles of individual cholangiocarcinoma organoids are different and do not cluster together. However, growth factor signaling (EGFR, PDGFRβ) and downstream effectors (MAPK pathway) are more active in cholangiocarcinoma organoids and could provide potential druggable targets. Screening of 31 kinase inhibitors revealed several promising pan-effective inhibitors and compounds that show patient-specific efficacy. Kinase inhibitor sensitivity correlated to the activity of its target kinases for several inhibitors, signifying them as potential predictors of response. Moreover, we identified correlations between drug response and kinases not directly targeted by those drugs.In conclusion, kinome profiling is a feasible method to identify druggable targets for cholangiocarcinoma. Future studies should confirm the potential of kinase activity profiles as biomarkers for patient stratification and precision medicine.

Kinome

Druggability

Organoid

Targeted Therapy

10.1186/s10020-022-00498-1

Cite

Citations (7)

Metabolismo de glicose em células leucemicas humanas

Alessandra Valéria de Sousa Faria

10.47749/t/unicamp.2016.975907

Cite

Citations (0)

Linhagens de células de melanoma: Mutações e impacto em vias de transdução de sinal / Melanoma cell lines: Mutations and impact on signal transduction pathways

Brazilian Journal of Health Review (2020)

Beatriz Aires Lopes Anderson Gabriel Ortelan Alessandra Valéria de Sousa Faria Carmen Veríssima Ferreira‐Halder

Linhagens de células de melanoma:

10.34119/bjhrv3n4-291

Cite

Citations (1)

Two-Step Purification of L-Asparaginase from Acrylaway® L

Figshare (2022)

Louise Lacalendola Tundisi D. Coelho Alessandra Valéria de Sousa Faria Adalberto Pessoa Elias Basile Tambourgi

Abstract L-Asparaginase (L-ASNase) is a biopharmaceutical used for acute lymphoblastic leukaemia (ALL) treatment, dramatically increasing the patients’ chance of cure. However, its production and distribution in developing countries were disrupted because of its low profitability, which caused great concern among patients. This study evaluates the feasibility of combining fractional precipitation and aqueous two-phase systems (ATPS) to purify L-ASNase from a low-grade product, commercially known as Acrylaway® L. The ATPS purification results were not particularly expressive compared to the two-step purification process composed of ethanol precipitation and gel filtration, which was able to recover the target molecule with a purification factor over 5 fold. Thus, we studied a purification process capable of manufacturing pharmaceutical grade L-ASNase from a commercially available low-grade raw material; however, improvements regarding its throughput must be achieved, and high purity is the first step to apply it as a new biopharmaceutical product. The proposed process could pose as a short-time solution to mitigate its shortage while a cost-effective production plant is being developed.

10.6084/m9.figshare.20455256

Cite

Citations (0)

Violacein negatively modulates the colorectal cancer survival and epithelial–mesenchymal transition

Journal of Cellular Biochemistry (2022)

Patrícia Fernandes de Souza Oliveira Alessandra Valéria de Sousa Faria Stefano Piatto Clerici Erica M. Akagi Hernandes F. Carvalho

Abstract Violacein is a secondary metabolite produced by several microorganisms including Chromobacterium violaceum , and it is already used in food and cosmetics. However, due to its potent anticancer and low side effects, its molecular action needs to be deeply scrutinized. Therefore, the main objective of this study was to evaluate the violacein's ability to interfere with three cancer hallmarks: growth factors receptor‐dependent signaling, proliferation, and epithelial–mesenchymal transition (EMT). Violacein has been associated with the induction of apoptosis in colorectal cancer (CRC) cells. Here, we demonstrate that this molecule is also active in CRC spheroids and inhibits cell migration. Violacein treatment reduced the amount of EGFR and AXL receptors in the HT29 cell line. Accordingly, the inhibition of the AKT, ERK, and PKCδ kinases, which are downstream mediators of the signaling pathways triggered by EGFR and AXL, is detected. Another interesting finding was that even when the cells were stimulated with transforming growth factor‐β, the EMT marker (N‐cadherin) decreased. Therefore, this study provides further evidence that reinforces the potential of violacein as an antitumor agent, once this biomolecule can “switch off” properties associated with cancer plasticity.

Cell Signaling

10.1002/jcb.30295

Cite

Citations (7)

AUTHOR INDEX

Journal of Biological Chemistry (2019)

Alessandro Achille Michael Adams Adamu Ishaku Ayodeji Asuni Bing Bai

10.1016/s0021-9258(20)34698-6

Cite

Citations (0)