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A Cancer Cell Spheroid Assay to Assess Invasion in a 3D Setting
Published on: November 20, 2015
Targeting the tetraspanin CD81 reduces cancer invasion and metastasis
Felipe Vences-Catalán1, Ranjani Rajapaksa1, Chiung-Chi Kuo1
1Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.
Abstract:
Tetraspanins are an evolutionary conserved family of proteins involved in multiple aspects of cell physiology, including proliferation, migration and invasion, protein trafficking, and signal transduction; yet their detailed mechanism of action is unknown. Tetraspanins have no known natural ligands, but their engagement by antibodies has begun to reveal their role in cell biology. Studies of tetraspanin knockout mice and of germline mutations in humans have highlighted their role under normal and pathological conditions. Previously, we have shown that mice deficient in the tetraspanin CD81 developed fewer breast cancer metastases compared to their wild-type (WT) counterparts. Here, we show that a unique anti-human CD81 antibody (5A6) effectively halts invasion of triple-negative breast cancer (TNBC) cell lines. We demonstrate that 5A6 induces CD81 clustering at the cell membrane and we implicate JAM-A protein in the ability of this antibody to inhibit tumor cell invasion and migration. Furthermore, in a series of in vivo studies we demonstrate that this antibody inhibits metastases in xenograft models, as well as in syngeneic mice bearing a mouse tumor into which we knocked in the human CD81 epitope recognized by the 5A6 antibody.
Insights
An anti-CD81 antibody (5A6) effectively inhibits triple-negative breast cancer (TNBC) cell invasion and migration. This antibody targets CD81 clustering and involves JAM-A protein, reducing metastasis in preclinical models.
Area of Science:
- Cell Biology
- Cancer Research
- Immunology
Background:
- Tetraspanins are conserved proteins regulating cell functions like migration and invasion.
- Their precise mechanisms remain unclear, but antibodies reveal their roles.
- Previous studies showed CD81 deficiency reduces breast cancer metastasis.
Purpose of the Study:
- To investigate the role of the tetraspanin CD81 in triple-negative breast cancer (TNBC) invasion.
- To evaluate the efficacy of a novel anti-CD81 antibody (5A6) in inhibiting TNBC cell invasion and metastasis.
Main Methods:
- Utilized anti-human CD81 antibody (5A6) on TNBC cell lines.
- Assessed CD81 clustering and JAM-A protein involvement.
- Conducted in vivo studies using xenograft and syngeneic mouse models.
Main Results:
- The 5A6 antibody effectively halted invasion of TNBC cell lines.
- 5A6 induced CD81 clustering and implicated JAM-A in inhibiting invasion and migration.
- In vivo studies demonstrated significant inhibition of metastases by the 5A6 antibody.
Conclusions:
- The anti-CD81 antibody 5A6 is a potent inhibitor of TNBC cell invasion and metastasis.
- Targeting CD81 clustering via 5A6, potentially involving JAM-A, offers a therapeutic strategy for TNBC.
- Further research into CD81-targeted therapies for breast cancer is warranted.
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