Adaptation of the group A <i>Streptococcus</i> adhesin Scl1 to bind fibronectin type III repeats within wound‐associated extracellular matrix: implications for cancer therapy

McNitt, Dudley H; Choi, Soo Jeon; Allen, Jessica L.; Hames, River A.; Weed, Scott A.; Water, Livingston Van De; Berisio, Rita; Łukomski, Sławomir

doi:10.1111/mmi.14317

Cited by 12 publications

(17 citation statements)

References 108 publications

(165 reference statements)

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“…Interestingly, the aforementioned extracellular matrix (ECM) proteins components are also constituents of tumor microenvironment and our initial experiments suggest Scl1 has the capacity for targeting solid tumors. These data collectively support the premise for utilization of the Scl1-FnIII interaction as a novel method of anti-neoplastic targeting in the tumor microenvironment [40].…”

Section: Resultssupporting

confidence: 68%

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

Ivanenko

2021

Med. Sci. of Ukr.

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Relevance. Treatment of solid tumors and biofilm-derived infections face a common problem: drugs often fail to reach and kill cancer cells and microbial pathogens because of local microenvironment heterogeneities. There are remarkable challenges for current and prospective anticancer and antibiofilm agents to target and maintain activity in the microenvironments where cancer cells and microbial pathogens survive and cause the onset of disease. Bacterial infections in cancer formation will increase in the coming years. Collection of approaches such as ROS modulation in cells, the tumor is promoted by microbe’s inflammation can be a strategy to target cancer and bacteria. Besides that, bacteria may take the advantage of oxygen tension and permissive carbon sources, therefore the tumor microenvironment (TM) becomes a potential refuge for bacteria. It is noteworthy that the relationship between cancer and bacteria is intertwined. Objective: To analyze similarities between biofilm and tumor milieu that is produced against stress conditions and heterogeneous microenvironment for a combination of approaches the bacteriotherapy with chemotherapy which can help in defeating the tumor heterogeneity accompanied with malignancy, drug-resistance, and metastasis. Method: An analytical review of the literature on keywords from the scientometric databases PubMed, Wiley. Results: Bacteria evade antimicrobial treatment is mainly due to persistence that has become dormant during the stationary phase and tolerance. Drug-tolerant persisters and cellular dormancy are crucial in the development of cancer, especially in understanding the development of metastases as a late relapse. Bioﬁlms are formed by groups of cells in diﬀerent states, growing or non-growing and metabolically active or inactive in variable fractions, depending on maturity and on chemical gradients (O2 and nutrients) of the bioﬁlms producing physiological heterogeneity. Heterogeneity in the microenvironment of cancer can be described as a non-cell autonomous driver of cancer cell diversity; in a highly diverse microenvironment, different cellular phenotypes may be selected for or against in different regions of the tumor. Hypoxia, oxidative stress, and inflammation have been identified as positive regulators of metastatic potential, drug resistance, and tumorigenic properties in cancer. It is proven that, Escherichia coli (E. coli) and life-threatening infectious pathogens such as Staphylococcus aureus (SA) and Mycobacterium tuberculosis (Mtb) are noticeably sensitive to alterations in the intracellular oxidative environment. An alternative emerging paradigm is that many cancers may be promoted by commensal microbiota, either by translocation and adherence of microbes to cancer cells or by the distant release of inflammation-activating microbial metabolites. Microbial factors such as F. nucleatum, B. fragilis, and Enterobacteriaceae members may contribute to disease onset in patients with a hereditary form of colorectal cancer (CRC); familial adenomatous polyposis (FAP). These findings are linked with the creation of new biomarkers and therapy for identifying and treating biofilm-associated cancers. Currently, about 20% of neoplasms globally can be caused by infections, with approximately 1.2 million cases annually. Several antineoplastic drugs that exhibited activity against S. mutans, including tamoxifen, doxorubicin, and ponatinib, also possessed activity against other Gram-positive bacteria. Drug repurposing, also known as repositioning, has gained momentum, mostly due to its advantages over de novo drug discovery, including reduced risk to patients due to previously documented clinical trials, lower drug development costs, and faster benchtop-to-clinic transition. Although many bacteria are carcinogens and tumor promoters, some have shown great potential towards cancer therapy. Several species of bacteria have shown an impressive power to penetrate and colonize solid tumors, which has mainly led to neoplasm slower growth and tumor clearance. Different strains of Clostridia, Lactococcus, Bifidobacteria, Shigella, Vibrio, Listeria, Escherichia, and Salmonella have been evaluated against cancer in animal models. Conclusion. Cancer is a multifactorial disease and the use of bacteria for cancer therapy as an immunostimulatory agent or as a vector for carrying the therapeutic cargo is a promising treatment method. Therefore, the world has turned to an alternative solution, which is the use of genetically engineered microorganisms; thus, the use of living bacteria targeting cancerous cells is the unique option to overcome these challenges. Bacterial therapies, whether used alone or combination with chemotherapy, give a positive effect to treat multiple conditions of cancer.

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Section: Resultssupporting

confidence: 68%

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

Ivanenko

2021

Med. Sci. of Ukr.

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“…This would not be the first report of GAS exhibiting mechanisms to ‘sense’ environmental processes. Previous observations found that by employing the major GAS surface protein SclA/Scl1, GAS can adapt and respond to the host’s wound environment by selectively binding wound associated isotypes of Fn (44). Future studies exploring the physiological impacts of antibody mediated binding of Fn to M protein could prove essential in better understanding the highly complex relationship between GAS and the immune system.…”

Section: Discussionmentioning

confidence: 99%

Group A streptococci induce high-affinity M protein-fibronectin interaction when specific human antibodies are bound

Wrighton

Ahnlide

André

et al. 2022

Preprint

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Group A streptococcus (GAS) is a highly adapted, human-specific pathogen that is known to manipulate the immune system through various mechanisms. GAS' M protein constitutes a primary target of the immune system due to its spatial configuration and dominance on the bacterial surface. Antibody responses targeting the M protein have been shown to favor the conserved C region. Such antibodies circumvent antigenic escape and efficiently bind to various M types. The ability of GAS to bind to fibronectin (Fn), a high molecular weight glycoprotein of the extracellular matrix, has long been known to be essential for the pathogen's evolutionary success and fitness. However, some strains lack the ability to efficiently bind Fn. Instead, they have been found to inefficiently bind Fn via the M protein A-B domains. Here, we show that human antibodies can induce a high-affinity Fn-binding state in M proteins, likely by enhancing the weak A-B domain binding. The antibodies bind to a conserved region of M proteins, and the high-affinity binding only occurs on the individual M proteins with bound specific antibodies. By allowing the binding of antibodies to a certain region in M, and thereby enhancing Fn-binding, GAS exploits the human humoral immune response to efficiently bind Fn without needing to waste energy on the production of additional proteins - potentially giving such strains an evolutionary advantage.

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“…Group A Streptococcus Streptococcal collagen-like protein 1 (Scl1), is a major GAS adhesin, which exhibits selective binding to ECM proteins [ 85 ]. Scl1 binds to tumor-associated isoforms of cellular fibronectin (cFn) containing type IIII repeats, extra domain A and/or B (EDA/EDB/cFn) also known as oncofetal Fn [ 86 , 87 , 88 ]. Binding to EDA and EDB is mediated through conserved structural determinants present within the Scl1 globular V domain and facilitates GAS adherence and biofilm formation in the host [ 89 , 90 , 91 ].…”

Section: Strategies For Targeting Fibrosis In Pdacmentioning

confidence: 99%

“…Binding to EDA and EDB is mediated through conserved structural determinants present within the Scl1 globular V domain and facilitates GAS adherence and biofilm formation in the host [ 89 , 90 , 91 ]. In vitro, Scl1 mediates biofilm formation on matrices deposited by cancer-associated fibroblasts (CAFs) and osteosarcoma (Saos-2) cells containing EDA/EDB/cFn isoforms [ 87 , 89 ]. Importantly, oncofetal cFn is expressed in many cancers [ 92 ], including pancreatic tumors [ 93 ], suggesting a potential for bacterial targeting of tumors by Scl1 after injection [ 94 ].…”

Section: Strategies For Targeting Fibrosis In Pdacmentioning

confidence: 99%

Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

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Adaptation of the group A Streptococcus adhesin Scl1 to bind fibronectin type III repeats within wound‐associated extracellular matrix: implications for cancer therapy

Cited by 12 publications

References 108 publications

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

Group A streptococci induce high-affinity M protein-fibronectin interaction when specific human antibodies are bound

Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

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