Article
Biochemistry & Molecular Biology
Albina Fejza, Maurizio Polano, Lucrezia Camicia, Evelina Poletto, Greta Carobolante, Giuseppe Toffoli, Maurizio Mongiat, Eva Andreuzzi
Summary: The study suggests that EMILIN-2 plays a role in the response to PD-L1 inhibitors in melanoma patients, with its absence associated with increased PD-L1 expression and improved immunotherapy efficacy. EMILIN-2 regulates PD-L1 expression in melanoma cells through immune-dependent mechanisms, impacting treatment outcomes and angiogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Eva Andreuzzi, Albina Fejza, Maurizio Polano, Evelina Poletto, Lucrezia Camicia, Greta Carobolante, Giulia Tarticchio, Federico Todaro, Emma Di Carlo, Melania Scarpa, Marco Scarpa, Alice Paulitti, Alessandra Capuano, Vincenzo Canzonieri, Stefania Maiero, Mara Fornasarig, Renato Cannizzaro, Roberto Doliana, Alfonso Colombatti, Paola Spessotto, Maurizio Mongiat
Summary: This study reveals the importance of EMILIN-2 in the development and prognosis of colorectal cancer. Loss of EMILIN-2 is associated with increased tumor numbers and altered immune cell populations in CRC models. Mechanistically, EMILIN-2 regulates macrophage polarization through the Toll-like Receptor 4/MyD88/NF-kappa B pathway. Furthermore, EMILIN-2 expression levels are correlated with the prognosis of CRC patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Sarah Watson, Nadege Gruel, Francois Le Loarer
Summary: RPS refers to a group of heterogeneous tumors originating from retroperitoneal tissues and vessels. Well-differentiated/dedifferentiated liposarcomas and leiomyosarcomas are the most common subtypes, but other rare histological subtypes can also be observed. Significant advances have been made in the pathological and molecular characterization of sarcomas, leading to changes in diagnostic management and the development of new therapeutic strategies based on tumor biology and microenvironment. This review summarizes the current knowledge and recent findings in the pathology and molecular biology of the most frequent RPS subtypes.
Review
Biochemistry & Molecular Biology
Stephan Niland, Johannes A. Eble
Summary: The tumor microenvironment (TME) is a key focus in cancer research and treatment, involving various components including ECM and modifying enzymes. Cells within the TME interact with the ECM, influencing tumor progression through feedback mechanisms involving cellular receptors, cytokines, and exosomes. Matrix remodeling in the TME, particularly by matrix metalloproteinases (MMPs), plays a crucial role in modifying ECM barriers and releasing soluble ECM fragments that impact cells both within and outside the TME.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Guido Carpino, Vincenzo Cardinale, Alessandra Di Giamberardino, Diletta Overi, Samantha Donsante, Tania Colasanti, Gaia Amato, Gianluca Mennini, Matteo Franchitto, Fabrizio Conti, Massimo Rossi, Mara Riminucci, Eugenio Gaudio, Domenico Alvaro, Carmine Mancone
Summary: The study identified THBS1, THBS2, and PEDF released in iCCA inhibit vessel growth and promote tumor-associated lymphangiogenesis, offering potential targets for interventions to counteract the dissemination process in iCCA.
JOURNAL OF HEPATOLOGY
(2021)
Article
Engineering, Biomedical
Samuel Alkmin, Manish S. Patankar, Paul J. Campagnola
Summary: Ovarian cancer is the deadliest gynecological cancer due to poor screening and imaging tools as well as limited understanding of the tumor microenvironment. This study used multiphoton excited fabrication to create orthogonal models representing the collagen matrix morphology and stiffness of normal ovarian stroma and high grade serous ovarian cancers. The study found that fiber morphology and matrix stiffness play important roles in migration and cytoskeletal dynamics of normal and cancer cells, and cell-specific differences highlight the importance of presenting both morphology and stiffness cues.
ACTA BIOMATERIALIA
(2022)
Article
Oncology
Bian Yanes, Elena Rainero
Summary: Mitochondria play essential roles in cellular functions, and dysfunctions have been observed in cancer. The interaction between cancer cells and the extracellular matrix (ECM) is crucial for tumor initiation and progression. Remodeling of ECM associated with tumorigenesis contributes to the regulation of mitochondrial function, promoting cancer cell metabolic plasticity that fuels invasion and metastasis.
Article
Oncology
Ancuta Jurj, Sergiu Pasca, Cornelia Braicu, Ioana Rusu, Schuyler S. Korban, Ioana Berindan-Neagoe
Summary: Organoids are simplified in vitro model systems of organs used for studying tissue development, disease, drug screening, cell therapy, and personalized medicine. They can self-renew and self-organize, while demonstrating similar organ functionality as the original tissue. Organoids provide significant opportunities for human biomedical research and reducing reliance on experimental animals.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Oncology
Hanna Nystrom
Summary: The tumor microenvironment (TME) has a significant impact on liver metastasis, with components including ECM playing a crucial role in the formation of metastatic organs.
SEMINARS IN CANCER BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Anna Buder, Ellen Heitzer, Julie Waldispuehl-Geigl, Sabrina Weber, Tina Moser, Maximilian J. Hochmair, Klaus Hackner, Peter Errhalt, Ulrike Setinek, Martin Filipits
Summary: The presence of resistance-related gene SCNAs in plasma before the initiation of osimertinib therapy is associated with lower response rate and shorter progression-free and overall survival.
Review
Immunology
Seung-Jin Kim, Dipendra Khadka, Jae Ho Seo
Summary: This article discusses the process of tumors adapting to adverse environments through communication with neighboring cells. Understanding the physiology of these tumors and their interaction with the tumor environment can help in developing promising tumor treatment strategies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Kendelle J. Murphy, Cecilia R. Chambers, David Herrmann, Paul Timpson, Brooke A. Pereira
Summary: PDAC is a highly lethal solid malignancy with a low five-year survival rate of around 10%. The interactions between tumor and stromal or immune cells in the pancreatic tumor microenvironment play a critical role in both promoting and restraining the development and progression of PDAC. Understanding the role of the extracellular matrix and stromal cells like cancer-associated fibroblasts (CAFs) is vital for developing effective treatment strategies for this aggressive disease.
Article
Biology
Samantha C. Schwager, Katherine M. Young, Lauren A. Hapach, Caroline M. Carlson, Jenna A. Mosier, Tanner J. McArdle, Wenjun Wang, Curtis Schunk, Anissa L. Jayathilake, Madison E. Bates, Francois Bordeleau, Marc A. Antonyak, Richard A. Cerione, Cynthia A. Reinhart-King
Summary: Weakly migratory cancer cells disseminate from the primary tumor via communication with stromal cells and enhance cancer cell migration and metastasis by releasing microvesicles rich in Tg2.
Review
Pharmacology & Pharmacy
Mohammad Khoonkari, Dong Liang, Marleen Kamperman, Frank A. E. Kruyt, Patrick van Rijn
Summary: The biology and physics of glioblastoma are not completely understood, leading to limited effectiveness of current clinical therapy. Mechanical stress plays an important role in the development and malignancy of cancer, including glioblastoma. Alterations in the extracellular matrix (ECM) of the brain and the resulting stiffening of the ECM affect signaling activity and contribute to the aggressive behavior of glioblastoma cells. Mechanosensing signaling pathways, such as Hippo/YAP, CD44, and actin skeleton signaling, play a role in remodeling the cytoskeleton and influencing cellular properties. Hydrogels are used to mimic the stiffening of the brain ECM in vitro. Understanding these processes could potentially lead to new therapeutic approaches for glioblastoma.
Article
Oncology
Tian-Gen Chang, Yingying Cao, Eldad D. Shulman, Uri Ben-David, Alejandro A. Schaffer, Eytan Ruppin
Summary: This study examined the ability of two common copy-number alteration (CNA) scores, AS and FGA, to predict survival following immunotherapy in 3139 patients with different cancer types. The results showed that AS and FGA could predict overall survival in both high-TMB and low-TMB patients, but their predictive power was limited to only a few specific cancer types. Larger sample sizes are needed to determine their clinical utility in other cancer types. Additionally, a simple elbow-point-based method was proposed to determine the cutoff for calling CNAs.
NPJ PRECISION ONCOLOGY
(2023)
Article
Anatomy & Morphology
Anna Barque, Kyleen Jan, Emanuel De La Fuente, Christina L. Nicholas, Richard O. Hynes, Alexandra Naba
Summary: The study revealed essential roles for SNED1 in mouse development and neonatal survival, with its knockout leading to craniofacial and skeletal defects. Human studies have shown that deletion of the 2q37.3 region, including the SNED1 locus, is associated with facial dysmorphism and short stature.
DEVELOPMENTAL DYNAMICS
(2021)
Article
Oncology
Elisa Holstein, Annalena Dittmann, Anni Kaariainen, Vilma Pesola, Jarkko Koivunen, Taina Pihlajaniemi, Alexandra Naba, Valerio Izzi
Summary: Mutations play a crucial role in the oncogenic process by altering regulatory pathways and leading to uncontrolled cell proliferation. While mutations in intracellular proteins are well understood, less is known about mutations in extracellular matrix-associated proteins. This study highlights the specificity of mutations affecting post-translational modification sites in the extracellular matrix and their potential impact on the tumor microenvironment.
Article
Biochemistry & Molecular Biology
Sylvain D. Vallet, Martin N. Davis, Anna Barque, Ali H. Thahab, Sylvie Ricard-Blum, Alexandra Naba
Summary: This study presents a novel ECM protein, SNED1, which promotes breast cancer metastasis and regulates craniofacial development. By combining computational predictions and experimental approaches, the physico-chemical properties of SNED1 were characterized, and its potential functions were inferred, shedding light on its pathophysiological roles.
BIOCHEMICAL JOURNAL
(2021)
Article
Endocrinology & Metabolism
Alexandra Pokhilko, Gaia Brezzo, Lahiru Handunnetthi, Raphael Heilig, Rachel Lennon, Colin Smith, Stuart M. Allan, Alessandra Granata, Sanjay Sinha, Tao Wang, Hugh S. Markus, Alexandra Naba, Roman Fischer, Tom Van Agtmael, Karen Horsburgh, M. Zameel Cader
Summary: This study successfully extracted cerebrovascular ECM from mouse and human brain tissues and identified over 1000 proteins in the ECM-enriched fraction. The identification of 147 core ECM proteins in the human brain vascular matrisome and the connection between brain ECM proteins and cerebrovascular diseases, provides unique mechanistic insight and potential drug targets for cerebrovascular diseases.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Cell Biology
Carine Renner, Clarissa Gomez, Mike R. Visetsouk, Isra Taha, Aisha Khan, Stephanie M. McGregor, Paul Weisman, Alexandra Naba, Kristyn S. Masters, Pamela K. Kreeger
Summary: Recent evidence supports the fimbriae of the fallopian tube as one origin site for high-grade serous ovarian cancer (HGSOC) and explores the ECM changes associated with STICs formation.
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2022)
Review
Biology
Bryan A. Nerger, Tia M. Jones, Keron W. J. Rose, Anna Barque, Justin S. Weinbaum, Ryan J. Petrie, Joan Chang, Davy Vanhoutte, Kendra LaDuca, Dirk Hubmacher, Alexandra Naba
Summary: The extracellular matrix (ECM) plays a crucial role in providing structural support and signaling to cells. Recent advances in ECM research include the use of model systems, targeting ECM for therapeutics, cell-ECM interactions, and tissue engineering strategies. The American Society for Matrix Biology (ASMB) also emphasized mentoring, career development, and diversity, equity, and inclusion initiatives in their events.
Article
Biochemical Research Methods
Kristin E. Burnum-Johnson, Thomas P. Conrads, Richard R. Drake, Amy E. Herr, Ravi Iyengar, Ryan T. Kelly, Emma Lundberg, Michael J. MacCoss, Alexandra Naba, Garry P. Nolan, Pavel A. Pevzner, Karin D. Rodland, Salvatore Sechi, Nikolai Slavov, Jeffrey M. Spraggins, Jennifer E. Van Eyk, Marc Vidal, Christine Vogel, David R. Walt, Neil L. Kelleher
Summary: Proteins play a crucial role in human diseases, but our current understanding and quantification abilities are limited. To overcome the challenges in protein biology, we present a projection of technologies for the next decade. By utilizing next-generation approaches, we aim to define, quantify, and visualize the proteome, leading to a transformation in our understanding and interactions with human diseases.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Biochemistry & Molecular Biology
Tristen V. Tellman, Merve Dede, Vikram A. Aggarwal, Duncan Salmon, Alexandra Naba, Mary C. Farach-Carson
Summary: The extracellular matrix (ECM) plays a crucial role in organ development and function, with alterations potentially leading to diseases. The analysis of transcriptome data from human samples provides new insights into the expression of ECM genes.
Article
Dermatology
Paulene Sapao, Elisha D. O. Roberson, Bo Shi, Shervin Assassi, Brian Skaug, Fred Lee, Alexandra Naba, Bethany E. Perez White, Carlos Cerdova-Fletes, Pei-Suen Tsou, Amr H. Sawalha, Johann E. Gudjonsson, Feiyang Ma, Priyanka Verma, Dibyendu Bhattacharyya, Mary Carns, Jerome F. Strauss III, Delphine Sicard, Daniel J. Tschumperlin, Melissa I. Champer, Paul J. Campagnola, Maria E. Teves, John Varga
Summary: Systemic sclerosis (SSc) is a fibrotic disease with no effective treatment. This study found that SPAG17 expression was downregulated in SSc patients and negatively correlated with fibrotic gene expression. Further experiments revealed that reduced chromatin accessibility at the SPAG17 locus was observed in SSc fibroblasts and endothelial cells. Knock-down of SPAG17 resulted in myofibroblast transformation and increased sensitivity to profibrotic stimuli. These findings provide important insights into the pathogenesis of SSc and suggest SPAG17 as a potential target for developing innovative therapies for fibrotic conditions.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Cell Biology
Chandrani Mondal, Majo J. Gacha-Garay, Kathryn A. Larkin, Rebecca C. Adikes, Julie S. Di Martino, Chen-Chi Chien, Madison Fraser, Ireti Eni-aganga, Esperanza Agullo-Pascual, Katarzyna Cialowicz, Umut Ozbek, Alexandra Naba, Angelo Gaitas, Tian-Ming Fu, Srigokul Upadhyayula, Eric Betzig, David Q. Matus, Benjamin L. Martin, Jose Javier Bravo-Cordero
Summary: In this study, srGAP1 is identified as a regulator of the proliferative-to-invasive switch in breast cancer cells. srGAP1low cells display a motile and invasive phenotype, facilitating the extravasation of cancer cells from blood vessels and attenuating tumor growth. Interestingly, a population of srGAP1low cells remain as solitary disseminated tumor cells in the lungs.
Editorial Material
Biochemistry & Molecular Biology
Suneel S. Apte, Alexandra Naba
Article
Biochemistry & Molecular Biology
Xinhao Shao, Clarissa D. Gomez, Nandini Kapoor, James M. Considine, Christopher Grams, Yu (Tom) Gao, Alexandra Naba
Summary: The extracellular matrix (ECM) is a complex assembly of proteins that provide structural support for cells, tissues, and organs. The use of mass-spectrometry-based proteomics has led to the development of MatrisomeDB, a comprehensive database that profiles the composition of ECM in various tissues. This recent update includes additional curated studies, enhanced data visualization, and an abstract-mining tool for enrichment analysis.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Biochemical Research Methods
Alexandra Naba
Summary: The extracellular matrix (ECM) is a complex assembly of proteins that form the structural scaffold of multicellular organisms and transmit signals regulating cellular phenotypes. Changes in ECM composition and structure are linked to diseases affecting all physiological systems. Proteomic approaches have been developed to decipher the ECM composition and identify disease biomarkers.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Romain Desert, Wei Chen, Xiaodong Ge, Hui Han, Zhuolun Song, Sukanta Das, Dipti Athavale, Grace Guzman, Alexandra Naba, Orlando Musso, Natalia Nieto
Article
Oncology
Julie S. Di Martino, Ana Rita Nobre, Chandrani Mondal, Isra Taha, Eduardo F. Farias, Elana J. Fertig, Alexandra Naba, Julio A. Aguirre-Ghiso, Jose Javier Bravo-Cordero
Summary: Cancer cells disseminate and seed in distant organs, remaining dormant before forming detectable metastases. Research shows that dormant cancer cells assemble an ECM niche enriched with type III collagen, which is essential for sustaining tumor dormancy. Disruption of tumor-derived type III collagen can restore tumor cell proliferation and lead to dormancy-to-reactivation transition.