Hyaluronic Acid Present in the Tumor Microenvironment Can Negate the Pro-apototic Effect of a Recombinant Fragment of Human Surfactant Protein D on Breast Cancer Cells

Murugaiah, Valarmathy; Agostinis, Chiara; Varghese, Praveen M.; Belmonte, Beatrice; Vieni, Salvatore; Alaql, Fanan A.; Alrokayan, Salman H.; Khan, Haseeb A.; Kaur, Anuvinder; Roberts, Thomas M.; Madan, Taruna; Bulla, Roberta; Kishore, Uday

doi:10.3389/fimmu.2020.01171

Cited by 14 publications

(14 citation statements)

References 57 publications

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“…HA is involved in cancer progression and is remarkably increased in BC versus in normal breast tissue (48). Clinically, HA may be associated with highly invasive BC.…”

Section: Glycosaminoglycans and Proteoglycansmentioning

confidence: 99%

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Zhao

Zheng

et al. 2021

Front. Oncol.

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Increasing evidence shows that the extracellular matrix (ECM) is an important regulator of breast cancer (BC). The ECM comprises of highly variable and dynamic components. Compared with normal breast tissue under homeostasis, the ECM undergoes many changes in composition and organization during BC progression. Induced ECM proteins, including fibrinogen, fibronectin, hyaluronic acid, and matricellular proteins, have been identified as important components of BC metastatic cells in recent years. These proteins play major roles in BC progression, invasion, and metastasis. Importantly, several specific ECM molecules, receptors, and remodeling enzymes are involved in promoting resistance to therapeutic intervention. Additional analysis of these ECM proteins and their downstream signaling pathways may reveal promising therapeutic targets against BC. These potential drug targets may be combined with new nanoparticle technologies. This review summarizes recent advances in functional nanoparticles that target the ECM to treat BC. Accurate nanomaterials may offer a new approach to BC treatment.

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“…HA is involved in cancer progression and is remarkably increased in BC versus in normal breast tissue (48). Clinically, HA may be associated with highly invasive BC.…”

Section: Glycosaminoglycans and Proteoglycansmentioning

confidence: 99%

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Zhao

Zheng

et al. 2021

Front. Oncol.

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“…DNA sequences coding for 8 Gly-X-Y repeats of collagen region, α-helical neck and CRD region of human SP-D were cloned under T7 promoter and expressed in Escherichia coli BL21 (λDE3) pLysS using construct pUK-D1 (25,26). Primary bacterial inoculum (25 ml) was grown in Luria-Bertani (LB) medium (500 ml) with 34 μg/ml chloramphenicol and 100 μg/ml ampicillin (Sigma-Aldrich) at 37°C until an OD600 of 0.6 was reached.…”

Section: Expression and Purification Of Rfhsp-dmentioning

confidence: 99%

Human Surfactant Protein D Binds S1 and Receptor Binding Domain of Spike protein and acts as an entry inhibitor of SARS-CoV-2 Pseudotyped viral particlesin vitro

Hsieh

Beirag

Murugaiah

et al. 2020

Preprint

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Human SP-D is a potent innate immune molecule whose presence at pulmonary mucosal surfaces allows immune surveillance role against pulmonary pathogens. Higher levels of serum SP-D have been reported in patients with severe acute respiratory syndrome coronavirus-1 (SARS-CoV). Studies have suggested the ability of human SP-D to recognise spike glycoprotein of SARS-CoV; its interaction with HCoV-229E strain leads to viral inhibition in human bronchial epithelial (16HBE) cells. Previous studies have reported that a recombinant fragment of human SP-D (rfhSP-D) composed of 8 Gly-X-Y repeats, neck and CRD region, can act against a range of viral pathogens including influenza A Virus and Respiratory Syncytial Virus in vitro, in vivo and ex vivo models. In this context, this study was aimed at examining the likely protective role of rfhSP-D against SARS-CoV-2 infection. rfhSP-D showed a dose-responsive binding to S1 spike protein of SARS-CoV-2 and its receptor binding domain. Importantly, rfhSP-D inhibited interaction of S1 protein with the HEK293T cells overexpressing Angiotensin Converting Enzyme 2. The protective role of rfhSP-D against SARS-CoV-2 infection as an entry inhibitor was further validated by the use of pseudotyped lentiviral particles expressing SARS-CoV-2 S1 protein; ~0.5 RLU fold reduction in viral entry was seen following rfhSP-D treatment (10 μg/ml). The results highlight the therapeutic potential of rfhSP-D in SARS-CoV-2 infection and merits pre-clinical studies in murine models.

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“…As rfhSP-D is known to induce apoptosis in cancer and immortalised cells (18,(20)(21)(22), the effect of rfhSP-D on Vero cells was assessed using MTT assay. rfhSP-D treatment had no significant effect on the viability of Vero cells (Supplementary figure 3).…”

Section: Rfhsp-d Treatment Inhibits Sars-cov-2 Infection and Replicationmentioning

confidence: 99%

“…The rfhSP-D used was expressed and purified from E. coli as described previously (18,19). Briefly, the pUK-D1 plasmid that codes for the 8 Gly-X-Y repeats, neck and CRD regions of human SP-D was transformed into Escherichia coli BL21 (λDE3) pLysS (Invitrogen).…”

Section: Expression and Purification Of A Recombinant Fragment Of Hummentioning

confidence: 99%

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A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples

Madan

Biswas

Varghese

et al. 2020

Preprint

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RationaleCOVID-19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known.ObjectiveThis study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2.MethodsrfhSP-D interaction with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR.Measurements and Main ResultsIn-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 5μM rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 μM). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 5μM rfhSP-D.ConclusionsThese results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication in-vitro.

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Hyaluronic Acid Present in the Tumor Microenvironment Can Negate the Pro-apototic Effect of a Recombinant Fragment of Human Surfactant Protein D on Breast Cancer Cells

Cited by 14 publications

References 57 publications

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Human Surfactant Protein D Binds S1 and Receptor Binding Domain of Spike protein and acts as an entry inhibitor of SARS-CoV-2 Pseudotyped viral particlesin vitro

A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples

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