Novel Insights into Membrane Targeting of B Cell Lymphoma

Winde, Charlotte M. de; Elfrink, Suraya; Spriel, Annemiek B. van

doi:10.1016/j.trecan.2017.04.006

Cited by 20 publications

(17 citation statements)

References 87 publications

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“…Tetraspanins are emerging therapeutic targets for cancers, as multiple family members (e.g., CD81, CD53, CD9, CD151, TSPAN8, and CD37) have been implicated in tumor initiation, promotion, and/or metastasis (de Winde et al, 2017;Vences-Catalán & Levy, 2018;Bonnet et al, 2019;Vences-Catalán et al, 2019). CD81, for example, is expressed in a variety of solid tumors and hematopoietic malignancies, and loss of CD81 inhibits the invasion and metastasis of melanoma, breast, and lung tumor cells (Vences-Catalán et al, 2015).…”

Section: Cd53-assisted B-cell Migrationmentioning

confidence: 99%

Open conformation of tetraspanins shapes interaction partner networks on cell membranes

et al. 2020

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Tetraspanins, including CD53 and CD81, regulate a multitude of cellular processes through organizing an interaction network on cell membranes. Here, we report the crystal structure of CD53 in an open conformation poised for partner interaction. The large extracellular domain (EC2) of CD53 protrudes away from the membrane surface and exposes a variable region, which is identified by hydrogen–deuterium exchange as the common interface for CD53 and CD81 to bind partners. The EC2 orientation in CD53 is supported by an extracellular loop (EC1). At the closed conformation of CD81, however, EC2 disengages from EC1 and rotates toward the membrane, thereby preventing partner interaction. Structural simulation shows that EC1‐EC2 interaction also supports the open conformation of CD81. Disrupting this interaction in CD81 impairs the accurate glycosylation of its CD19 partner, the target for leukemia immunotherapies. Moreover, EC1 mutations in CD53 prevent the chemotaxis of pre‐B cells toward a chemokine that supports B‐cell trafficking and homing within the bone marrow, a major CD53 function identified here. Overall, an open conformation is required for tetraspanin–partner interactions to support myriad cellular processes.

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Section: Cd53-assisted B-cell Migrationmentioning

confidence: 99%

Open conformation of tetraspanins shapes interaction partner networks on cell membranes

et al. 2020

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“…To overcome this issue and when planning antibody-mediated therapy, attention was prioritized to a set of normal molecules, whose quantitative distribution may balance a tissue-dependent generalized expression. The experience and the clinical success obtained with anti-CD20 mAbs revitalized the interest in this strategy [ 3 ]. Similar strategies were applied for therapeutic targeting of CD22 [ 4 ].…”

Section: Premisementioning

confidence: 99%

The Circular Life of Human CD38: From Basic Science to Clinics and Back

et al. 2020

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Monoclonal antibodies (mAbs) were initially considered as a possible “magic bullet” for in vivo elimination of tumor cells. mAbs represented the first step: however, as they were murine in nature (the earliest experience on the field), they were considered unfit for human applications. This prompted the development of techniques for cloning the variable regions of conventional murine antibodies, genetically mounted on human IgG. The last step in this years-long process was the design for the preparation of fully human reagents. The choice of the target molecule was also problematic, since cancer-specific targets are quite limited in number. To overcome this obstacle in the planning phases of antibody-mediated therapy, attention was focused on a set of normal molecules, whose quantitative distribution may balance a tissue-dependent generalized expression. The results and clinical success obtained with anti-CD20 mAbs revived interest in this type of strategy. Using multiple myeloma (MM) as a tumor model was challenging first of all because the plasma cells and their neoplastic counterpart eluded the efforts of the Workshop on Differentiation Antigens to find a target molecule exclusively expressed by these cells. For this reason, attention was turned to surface molecules which fulfill the requisites of being reasonably good targets, even if not specifically restricted to tumor cells. In 2009, we proposed CD38 as a MM target in virtue of its expression: it is absent on early hematological progenitors, has variable but generalized limited expression by normal cells, but is extremely high in plasma cells and in myeloma. Further, regulation of its expression appeared to be dependent on a variety of factors, including exposure to all-trans retinoic acid (ATRA), a potent and highly specific inducer of CD38 expression in human promyelocytic leukemia cells that are now approved for in vivo use. This review discusses the history of human CD38, from its initial characterization to its targeting in antibody-mediated therapy of human myeloma.

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“…Several tetraspanins used as therapeutic targets show promise in preclinical models of tumor progression and metastases ( 7 , 28 , 55 , 83 ). However, CD37 is the only tetraspanin target that has moved forward into the clinic ( 84 ). CD37 is predominantly and abundantly expressed on mature B cell malignancies, but not on solid tumors.…”

Section: From Bench To Bedsidementioning

confidence: 99%

Immune Targeting of Tetraspanins Involved in Cell Invasion and Metastasis

Vences-Catalán

Levy

2018

Front. Immunol.

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Metastasis is the ultimate consequence of cancer progression and the cause of patients’ death across different cancer types. Patients with initial diagnosis of distant disease have a worst 5-year survival compared to patients with localized disease. Therapies that target primary tumors fail to eradicate distant dissemination of cancer. Recently, immunotherapies have improved the survival of patients with metastatic disease, such as melanoma and lung cancer. However, only a fraction of patients responds to immunotherapy modalities that target the host immune system. The need to identify new druggable targets that inhibit or prevent metastasis is, therefore, much needed. Tetraspanins have emerged as key players in regulating cell migration, invasion, and metastasis. By serving as molecular adaptors that cluster adhesion receptors, signaling molecules, and cell surface receptors; tetraspanins are involved in all steps of the metastatic cascade. They regulate cell proliferation, participate in EMT transition, modulate integrin-mediated cell adhesion, and participate in angiogenesis and invasion processes. Tetraspanins have also been shown to modulate metastasis indirectly through exosomes and by regulating cellular interactions in the immune system. Importantly, targeting individual tetraspanin with antibodies has impacted tumor progression. This review will focus on the contribution of tetraspanins to the metastatic process and their potential as therapeutic tumor targets.

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Novel Insights into Membrane Targeting of B Cell Lymphoma

Cited by 20 publications

References 87 publications

Open conformation of tetraspanins shapes interaction partner networks on cell membranes

Open conformation of tetraspanins shapes interaction partner networks on cell membranes

The Circular Life of Human CD38: From Basic Science to Clinics and Back

Immune Targeting of Tetraspanins Involved in Cell Invasion and Metastasis

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