Structural subunit organization of molluscan hemocyanins

Paccagnella, Martina; Bologna, L; Beccaro, M; Mičetić, Ivan; Muro, Paolo Di; Salvato, Benedetto

doi:10.1016/j.micron.2003.10.007

Cited by 6 publications

(6 citation statements)

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“…The knowledge of the carbohydrate moieties present in mollusk hemocyanins has been essential for understanding their organization, antigenicity and biomedical properties [33]–[35]. Some hemocyanins possess sugar moieties, such as mannose-rich oligosaccharides and the Thomsen-Friedenreich antigen disaccharide (T antigen disaccharide Galβ1-3GalNAcα1-Ser/Thr), which may play roles in their immune-related properties [36], [37].…”

Section: Resultsmentioning

confidence: 99%

A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma

et al. 2014

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Hemocyanins, the huge oxygen-transporting glycoproteins of some mollusks, are used as immunomodulatory proteins with proven anti-cancer properties. The biodiversity of hemocyanins has promoted interest in identifying new anti-cancer candidates with improved immunological properties. Hemocyanins promote Th1 responses without known side effects, which make them ideal for long-term sustained treatment of cancer. In this study, we evaluated a novel hemocyanin from the limpet/gastropod Fissurella latimarginata (FLH). This protein has the typical hollow, cylindrical structure of other known hemocyanins, such as the keyhole limpet hemocyanin (KLH) and the Concholepas hemocyanin (CCH). FLH, like the KLH isoforms, is composed of a single type of polypeptide with exposed N- and O-linked oligosaccharides. However, its immunogenicity was significantly greater than that of KLH and CCH, as FLH induced a stronger humoral immune response and had more potent anti-tumor activity, delaying tumor growth and increasing the survival of mice challenged with B16F10 melanoma cells, in prophylactic and therapeutic settings. Additionally, FLH-treated mice demonstrated increased IFN-γ production and higher numbers of tumor-infiltrating CD4+ lymphocytes. Furthermore, in vitro assays demonstrated that FLH, but not CCH or KLH, stimulated the rapid production of pro-inflammatory cytokines (IL-6, IL-12, IL-23 and TNF-α) by dendritic cells, triggering a pro-inflammatory milieu that may explain its enhanced immunological activity. Moreover, this effect was abolished when deglycosylated FLH was used, suggesting that carbohydrates play a crucial role in the innate immune recognition of this protein. Altogether, our data demonstrate that FLH possesses increased anti-tumor activity in part because it activates a more potent innate immune response in comparison to other known hemocyanins. In conclusion, FLH is a potential new marine adjuvant for immunization and possible cancer immunotherapy.

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Section: Resultsmentioning

confidence: 99%

A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma

et al. 2014

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“…Today, the information regarding the carbohydrate moiety composition is essential for understanding the mollusk hemocyanin organization, antigenicity and their biomedical properties [57,58]. Concerning that DCs play a pivotal role in the generation of antitumor immune response, recently it has been proposed that KLH induce the maturation of DCs through their interaction with lectin-receptors, like mannose receptor [59].…”

Section: Discussionmentioning

confidence: 99%

Immunodominant role of CCHA subunit of Concholepas hemocyanin is associated with unique biochemical properties

Becker

Fuentes

Campo

et al. 2009

International Immunopharmacology

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“…In addition, the carbohydrate moieties present in molluscan hemocyanins are considered responsible for their high immunogenicity. The carbohydrate structures of hemocyanins have been extensively studied in order to understand their organization, antigenicity, and biomedical properties [ 9 , 10 ]. The carbohydrate component of hemocyanins have been reported to be up to 9% ( w / w ) and contain diverse sugar moieties, including mannose, d -galactose, fucose, N-acetyl- d -galactosamine, and N-acetyl-glucosamine residues, as well as xylose, which is not usually present in animal proteins [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Hemocyanins from Helix and Rapana Snails Exhibit in Vitro Antitumor Effects in Human Colorectal Adenocarcinoma

et al. 2020

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Hemocyanins are oxygen-transporting glycoproteins in the hemolymph of arthropods and mollusks that attract scientific interest with their diverse biological activities and potential applications in pharmacy and medicine. The aim of the present study was to assess the in vitro antitumor activity of hemocyanins isolated from marine snail Rapana venosa (RvH) and garden snails Helix lucorum (HlH) and Helix aspersa (HaH), as well the mucus of H. aspersa snails, in the HT-29 human colorectal carcinoma cell line. The effects of the hemocyanins on the cell viability and proliferation were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the alterations in the tumor cell morphology were examined by fluorescent and transmission electron microscopy. The results of the MTT assay showed that the mucus and α-subunit of hemocyanin from the snail H. aspersa had the most significant antiproliferative activity of the tested samples. Cytomorphological analysis revealed that the observed antitumor effects were associated with induction of apoptosis in the tumor cells. The presented data indicate that hemocyanins and mucus from H. aspersa have an antineoplastic activity and potential for development of novel therapeutics for treatment of colorectal carcinoma.

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Structural subunit organization of molluscan hemocyanins

Cited by 6 publications

References 1 publication

A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma

A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma

Immunodominant role of CCHA subunit of Concholepas hemocyanin is associated with unique biochemical properties

Hemocyanins from Helix and Rapana Snails Exhibit in Vitro Antitumor Effects in Human Colorectal Adenocarcinoma

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