A peptide binding to the tetraspanin CD9 reduces cancer metastasis

Suwatthanarak, Thanawat; Ito, Kazuma; Tanaka, Masayoshi; Sugiura, Kei; Hoshino, Ayuko; Miyamoto, Yoshitaka; Miyado, Kenji; Okochi, Mina

doi:10.1016/j.bioadv.2023.213283

Cited by 6 publications

(6 citation statements)

References 42 publications

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“…As anti-human CD81 antibody (5A6) was previously reported to reduce tumor growth and metastasis in vivo by inhibiting cancer cell migration and invasion [ 14 ], P152, with comparable anti-migratory ability to 5A6, would be one of the promising biomolecules for cancer therapy. According to our previously screened CD9-binding peptides, the observation by high-resolution confocal microscopy suggested that the peptides directly bound to CD9 expressed on the cell surface [ 29 ]. Thus, we hypothesize that P152 in this study has the same potential to directly bind to CD81 expressed on the cell surface and then inhibit cancer cell migration.…”

Section: Resultsmentioning

confidence: 99%

“…Further P152-based modification and functionalization, such as sequence optimization and structure modification, may enhance its anti-migration potency [ 30 ]. P152 suppressing cancer cell migration may reduce the metastasis ability of cancer cells [ 29 ]. Because tetraspanin CD81 protein is one of the biomarkers for extracellular vesicles, P152 may also be applicable for targeting or collecting extracellular vesicles.…”

Section: Resultsmentioning

confidence: 99%

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Screening of EWI-2-Derived Peptides for Targeting Tetraspanin CD81 and Their Effect on Cancer Cell Migration

et al. 2023

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CD81, a transmembrane protein belonging to the tetraspanin family, has recently been suggested as a therapeutic target for cancers. Here, we screened peptides that bind to the tetraspanin CD81 protein, and evaluated their inhibitory activity in cancer cell migration. To screen for CD81-binding peptides (CD81-BP), a peptide array membrane was prepared from the amino acid sequence of the EWI-2 protein, a major partner of CD81, before binding to fluorescently labeled CD81. As a result, four candidate CD81-BPs were identified and characterized. In particular, the CFMKRLRK peptide (called P152 in this study) was found to be the best candidate that preferentially binds to the extracellular loop of CD81, with an estimated dissociation constant of 0.91 µM. Since CD81 was reported to promote cancer cell migration, an initial step in metastasis, the Boyden chamber assay, was next performed to assess the effect of CD81-BP candidates on the migration of MDA-MB-231 human breast cancer cells. Interestingly, our result indicated that P152 could suppress MDA-MB-231 cell migration at the level comparable to that of an anti-human CD81 antibody (5A6). Thus, we propose these CD81-BPs with the anti-migration property against cancer cells for the development of novel therapeutic strategies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Screening of EWI-2-Derived Peptides for Targeting Tetraspanin CD81 and Their Effect on Cancer Cell Migration

et al. 2023

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“…The same group successfully reduced melanoma lung metastasis after peptide binding to tetraspanin CD9. The CD9-binding peptide impeded tetraspanin web formation, cancer cell invasion and significantly reduced secretion and uptake of cancer cell exosomes (83). Antibody targeting of CD9 in pancreatic cancer disrupted CD9/ ADAM interactions and led to decreased proliferation, migration and colony formation (84).…”

Section: Tumor-promoting Propertiesmentioning

confidence: 99%

Prognostic value and multifaceted roles of tetraspanin CD9 in cancer

et al. 2023

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CD9 is a crucial regulator of cell adhesion in the immune system and plays important physiological roles in hematopoiesis, blood coagulation or viral and bacterial infections. It is involved in the transendothelial migration of leukocytes which might also be hijacked by cancer cells during their invasion and metastasis. CD9 is found at the cell surface and the membrane of exosomes affecting cancer progression and therapy resistance. High expression of CD9 is mostly associated with good patients outcome, with a few exceptions. Discordant findings have been reported for breast, ovarian, melanoma, pancreatic and esophageal cancer, which might be related to using different antibodies or inherent cancer heterogeneity. According to in vitro and in vivo studies, tetraspanin CD9 is not clearly associated with either tumor suppression or promotion. Further mechanistic experiments will elucidate the role of CD9 in particular cancer types and specific conditions.

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“…CD9, a member of the tetraspanin family, has been generally known for its participation in numerous biological activities, such as cell migration, adhesion, and communications [ 86 , 87 , 88 ]. In recent years, CD9 was found to play a role in cellular senescence by the involvement in the phosphatidylinositide 3 kinase-AKT-mTOR-p53 signal pathway [ 89 ].…”

Section: Targeted Sensing Senescence With Antibody-functionalized And...mentioning

confidence: 99%

Molecularly Targeted Fluorescent Sensors for Visualizing and Tracking Cellular Senescence

He,

Xu,

et al. 2023

Biosensors

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Specific identification and monitoring of senescent cells are essential for the in-depth understanding and regulation of senescence-related life processes and diseases. Fluorescent sensors providing real-time and in situ information with spatiotemporal resolution are unparalleled tools and have contributed greatly to this field. This review focuses on the recent progress in fluorescent sensors for molecularly targeted imaging and real-time tracking of cellular senescence. The molecular design, sensing mechanisms, and biological activities of the sensors are discussed. The sensors are categorized by the types of markers and targeting ligands. Accordingly, their molecular recognition and fluorescent performance towards senescence biomarkers are summarized. Finally, the perspective and challenges in this field are discussed, which are expected to assist future design of next-generation sensors for monitoring cellular senescence.

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A peptide binding to the tetraspanin CD9 reduces cancer metastasis

Cited by 6 publications

References 42 publications

Screening of EWI-2-Derived Peptides for Targeting Tetraspanin CD81 and Their Effect on Cancer Cell Migration

Screening of EWI-2-Derived Peptides for Targeting Tetraspanin CD81 and Their Effect on Cancer Cell Migration

Prognostic value and multifaceted roles of tetraspanin CD9 in cancer

Molecularly Targeted Fluorescent Sensors for Visualizing and Tracking Cellular Senescence

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