Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell–derived ADAM9

Mammadova‐Bach, Elmina; Zigrino, Paola; Brucker, Camille; Bourdon, Catherine; Freund, Monique; Arcangelis, Adèle De; Abrams, Scott I.; Orend, Gertraud; Gachet, Christian; Mangin, P

doi:10.1172/jci.insight.88245

Cited by 88 publications

(54 citation statements)

References 57 publications

(74 reference statements)

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“…Lin et al also found that the in vivo inhibition of ADAM9 protein expression on lung cancer cells decreased brain metastasis by enhancing the tissue plasminogen activator. 26 Mammadova-Bach et al 32 showed that the interplay between platelet α6β1 and tumour cell-expressed ADAM9 promotes efficient lung metastasis. ADAM9 overexpression portends a poor prognosis for patients with non-small cell lung cancer.…”

Section: Discussionmentioning

confidence: 99%

ADAM9 expression promotes an aggressive lung adenocarcinoma phenotype

et al. 2017

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A disintegrin and metalloproteinase 9 (ADAM9) possesses potent metastasis-inducing capacities and is highly expressed in several cancer cells. Previous work has shown that ADAM9 participates in the adhesive-invasive phenotype in lung cancer cells in vitro. In this study, we evaluated whether ADAM9 expression plays a critical role in metastatic processes in vivo and in angiogenesis. We first found that high ADAM9 expression was correlated with poor lung adenocarcinoma patient prognosis on Prognoscan data base. In vivo model based on intravenous injection in nude mice showed that a stable downregulation of ADAM9 in A549 (TrA549 A9-) cells was associated with a lower number of nodules in the lung, suggesting lower potentials for extravasation and metastasis. On a subcutaneous xenograft we showed that TrA549 A9- produced significantly smaller tumours and exhibited fewer neovessels. In addition, in vitro human umbilical vein endothelial cells exposed to supernatant from TrA549 A9- could reduce the formation of more vessel-like structures. To further understand the mechanism, a human antibody array analysis confirmed that five cytokines were downregulated in TrA549 A9- cells. Interleukin 8 was the most significantly downregulated, and its interaction with CXCR2 was implicated in angiogenesis on an in vitro model. These results emphasize the critical influence of ADAM9 on lung cancer progression and aggressiveness. ADAM9 should at least be a marker of cancer aggressiveness and a potential therapeutic target for cancer treatment.

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Section: Discussionmentioning

confidence: 99%

ADAM9 expression promotes an aggressive lung adenocarcinoma phenotype

et al. 2017

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“…On the other hand, the low expression of ADAM9 on tumor cells also impedes the interaction between platelets and tumor cells in breast cancer and melanoma. The interaction between ADAM9 and integrin β1 has been proven in several studies, which suggests that ADAM9 may have a role in platelet-mediated metastasis [ 119 ] ( Figure 2 ).…”

Section: Adam9 In the Tumor Microenvironmentmentioning

confidence: 99%

An Overview of ADAM9: Structure, Activation, and Regulation in Human Diseases

Chou

Huang

Kuo

et al. 2020

IJMS

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ADAM9 (A disintegrin and a metalloprotease 9) is a membrane-anchored protein that participates in a variety of physiological functions, primarily through the disintegrin domain for adhesion and the metalloprotease domain for ectodomain shedding of a wide variety of cell surface proteins. ADAM9 influences the developmental process, inflammation, and degenerative diseases. Recently, increasing evidence has shown that ADAM9 plays an important role in tumor biology. Overexpression of ADAM9 has been found in several cancer types and is correlated with tumor aggressiveness and poor prognosis. In addition, through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies. In this review, we summarize the current understanding of ADAM9 in biological function, pathophysiological diseases, and various cancers. Recent advances in therapeutic strategies using ADAM9-related pathways are presented as well.

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“…This shielding activity also promotes transendothelial extravasation of tumor cells at secondary sites . Defective platelet function or reducing platelet counts was able to strongly inhibit tumor metastasis in various transgenic mouse models . Nevertheless, the severe bleeding complication has limited the clinical utility of antiplatelet strategies .…”

Section: Nanoparticle‐mediated Tumor Vessel Targetingmentioning

confidence: 99%

Modulating the tumor microenvironment with new therapeutic nanoparticles: A promising paradigm for tumor treatment

Zhang

et al. 2019

Medicinal Research Reviews

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To better make nanomedicine entering the clinic, developing new rationally designed nanotherapeutics with a deeper understanding of tumor biology is required. The tumor microenvironment is similar to the inflammatory response in a healing wound, the milieu of which promotes tumor cell invasion and metastasis. Successful targeting of the microenvironmental components with effective nanotherapeutics to modulate the tumor microvessels or restore the homeostatic mechanisms in the tumor stroma will offer new hope for cancer treatment. We here highlight the progress in constructing nanotherapeutics to target or modulate the tumor microenvironment. We discuss the factors necessary for nanomedicines to become a new paradigm in cancer therapy, including the selection of drugs and therapeutic targets, controllable synthesis, and tempo-spatial drug release. K E Y W O R D S drug delivery, nanotherapeutics, therapeutic targets, tumor microenvironment Guangjun Nie and Suping Li are co-corresponding authors.Yinlong Zhang and Shih-Hsin Ho contributed equally to this work.

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Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell–derived ADAM9

Cited by 88 publications

References 57 publications

ADAM9 expression promotes an aggressive lung adenocarcinoma phenotype

ADAM9 expression promotes an aggressive lung adenocarcinoma phenotype

An Overview of ADAM9: Structure, Activation, and Regulation in Human Diseases

Modulating the tumor microenvironment with new therapeutic nanoparticles: A promising paradigm for tumor treatment

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