Soluble CD146 is a predictive marker of pejorative evolution and of sunitinib efficacy in clear cell renal cell carcinoma

Dufies, Maeva; Nollet, Marie; Traboulsi, Waël; Viotti, Julien; Borchiellini, Delphine; Grépin, Renaud; Parola, Julien; Giuliano, Sandy; Helley-Russick, Dominique; Bensalah, Karim; Ravaud, Alain; Bernhard, Jean-Christophe; Schiappa, Renaud; Bardin, Nathalie; Dignat-George, Françoise; Rioux‐Leclercq, Nathalie; Oudard, Stéphane; Négrier, Sylvie; Ferrero, Jean-­Marc; Chamorey, Emmanuel; Blot‐Chabaud, Marcel; Pagès, Gilles

doi:10.7150/thno.23002

Cited by 14 publications

(10 citation statements)

References 33 publications

(42 reference statements)

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“…Serum sCD146 is generally known to be a marker that reflects the severity of cardiovascular diseases and tumor development 30, 53, 54. An abnormal elevation in serum sCD146 has been reported to be correlated with the activity of ECs.…”

Section: Discussionmentioning

confidence: 99%

Soluble CD146, a cerebrospinal fluid marker for neuroinflammation, promotes blood-brain barrier dysfunction

Wang¹,

Duan²,

Feng³

et al. 2020

Theranostics

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The blood-brain barrier (BBB) dysfunction is an initial event of various neuroinflammatory diseases. However, the absence of reliable markers and mechanisms for BBB damage greatly limits the diagnosis and treatment of neuroinflammatory diseases. Soluble CD146 (sCD146) is mainly derived from vascular endothelial cells (ECs) and highly elevated in inflammatory settings. Based on a small cohort, our previous study showed that sCD146 is elevated in the cerebrospinal fluid (CSF) of multiple sclerosis (MS), which is accompanied with BBB damage. Nevertheless, whether sCD146 monitors and regulates the BBB dysfunction remains unknown.Methods: Coupled serum and CSF samples from patients with or without neuroinflammatory diseases were collected via multicenter collaborations. sCD146 was measured by sandwich ELISA using anti-CD146 antibodies AA1 and AA98, both of which were generated in our laboratory. The correlations between sCD146 and other clinical parameters or inflammatory factors were analyzed by Spearman's correlation coefficient analysis. The role of sCD146 on BBB function was examined in an in vitro BBB model.Results: Between July 20, 2011, and February 31, 2017, we collected coupled serum and CSF samples from 823 patients, of which 562 (68.3%) had neuroinflammatory diseases, 44 (5.3%) had remitting MS, and 217 (26.4%) had non-inflammatory neurological diseases (NIND). We found that sCD146 in CSF, but not in serum, is abnormally elevated in neuroinflammatory diseases (37.3 ± 13.3 ng/mL) compared with NIND (4.7 ± 2.9 ng/mL) and remitting MS (4.6 ± 3.5 ng/mL). Abnormally elevated CSF sCD146 is significantly correlated with the hyperpermeability-related clinical parameters of BBB and neuroinflammation-related factors. Moreover, CSF sCD146 shows higher sensitivity and specificity for evaluating BBB damage. Using an in vitro BBB model, we found that sCD146 impairs BBB function by promoting BBB permeability via an association with integrin αvβ1. Blocking integrin αvβ1 significantly attenuates sCD146-induced hyperpermeability of the BBB.Conclusion: Our study provides convincing evidence that CSF sCD146 is a sensitive marker of BBB damage and neuroinflammation. Furthermore, sCD146 is actively involved in BBB dysfunction.

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Section: Discussionmentioning

confidence: 99%

Soluble CD146, a cerebrospinal fluid marker for neuroinflammation, promotes blood-brain barrier dysfunction

Wang¹,

Duan²,

Feng³

et al. 2020

Theranostics

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“…We demonstrated that CD146 contributed to asthma pathogenesis in a mouse model. CD146 is not only expressed on the cell membrane but could also be released into circulation (33). To demonstrate the clinical significance of the study, we measured soluble CD146 (sCD146) levels in the plasma of asthma patients.…”

Section: Soluble Cd146 Was Elevated In the Plasma Of Asthma Patientsmentioning

confidence: 99%

Epithelial-Mesenchymal Transition in Asthma Airway Remodeling Is Regulated by the IL-33/CD146 Axis

Sun

et al. 2020

Front. Immunol.

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Epithelial-mesenchymal transition (EMT) is essential in asthma airway remodeling. IL-33 from epithelial cells is involved in pulmonary fibrosis. CD146 has been extensively explored in cancer-associated EMT. Whether IL-33 regulates CD146 in the EMT process associated with asthma airway remodeling is still largely unknown. We hypothesized that EMT in airway remodeling was regulated by the IL-33/CD146 axis. House dust mite (HDM) extract increased the expression of IL-33 and CD146 in epithelial cells. Increased expression of CD146 in HDM-treated epithelial cells could be blocked with an ST2-neutralizing antibody. Moreover, HDM-induced EMT was dependent on the CD146 and TGF-β/SMAD-3 signaling pathways. IL-33 deficiency decreased CD146 expression and alleviated asthma severity. Similarly, CD146 deficiency mitigated EMT and airway remodeling in a murine model of chronic allergic airway inflammation. Furthermore, CD146 expression was significantly elevated in asthma patients. We concluded that IL-33 from HDM extract-treated alveolar epithelial cells stimulated CD146 expression, promoting EMT in airway remodeling in chronic allergic inflammation.

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“…Clinically, CD146 surface expression positively correlates with resistance to some chemotherapies. For instance, it has been shown that the 786-O renal cell carcinoma robustly increases membrane CD146 expression together with the soluble form of this protein in the culture media as the cultured cells become resistant to Sunitinib, a tyrosine kinase inhibitor [ 76 ]. These resistant cells, referred to as 786-R, showed higher metastatic and invasive potentials as compared to 786-O cells.…”

Section: Cd146 In Pathological Angiogenesismentioning

confidence: 99%

Role of CD146 (MCAM) in Physiological and Pathological Angiogenesis—Contribution of New Antibodies for Therapy

et al. 2020

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The fundamental role of cell adhesion molecules in mediating various biological processes as angiogenesis has been well-documented. CD146, an adhesion molecule of the immunoglobulin superfamily, and its soluble form, constitute major players in both physiological and pathological angiogenesis. A growing body of evidence shows soluble CD146 to be significantly elevated in the serum or interstitial fluid of patients with pathologies related to deregulated angiogenesis, as autoimmune diseases, obstetric and ocular pathologies, and cancers. To block the undesirable effects of this molecule, therapeutic antibodies have been developed. Herein, we review the multifaceted functions of CD146 in physiological and pathological angiogenesis and summarize the interest of using monoclonal antibodies for therapeutic purposes.

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Soluble CD146 is a predictive marker of pejorative evolution and of sunitinib efficacy in clear cell renal cell carcinoma

Cited by 14 publications

References 33 publications

Soluble CD146, a cerebrospinal fluid marker for neuroinflammation, promotes blood-brain barrier dysfunction

Soluble CD146, a cerebrospinal fluid marker for neuroinflammation, promotes blood-brain barrier dysfunction

Epithelial-Mesenchymal Transition in Asthma Airway Remodeling Is Regulated by the IL-33/CD146 Axis

Role of CD146 (MCAM) in Physiological and Pathological Angiogenesis—Contribution of New Antibodies for Therapy

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