CD146: the unveiling of a pro-angiogenic netrin receptor

Croix, Brad St.

doi:10.1038/cr.2015.42

Cited by 9 publications

(8 citation statements)

References 12 publications

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“…CD146 has been reported to not be expressed by normal or reactive mesothelium and is currently expressed in normal conditions by vascular endothelial cells and smooth muscle cells, with a recently identified role in the promotion of angiogenesis. 15,34,35 In this study, we confirmed that this surface marker is highly expressed by primary cells isolated from pleural liquid of patients affected by MPM and by two commercially available MPM cell lines. In addition, we also observed that MPM biopsies express CD146 while normal/reactive mesothelium is negative for this marker.…”

Section: Discussionsupporting

confidence: 77%

<p>Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study</p>

Cova

Pandolfi

Colombo

et al. 2019

IJN

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PurposeMalignant pleural mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis. Its incidence is steadily increasing due to widespread asbestos exposure. There is still no effective therapy for MPM. Pemetrexed (Pe) is one of the few chemotherapeutic agents approved for advanced-stage disease, although the objective response to the drug is limited. The use of gold nanoparticles (GNPs) as a drug delivery system promises several advantages, including specific targeting of malignant cells, with increased intracellular drug accumulation and reduced systemic toxicity, and, in the case of MPM, direct treatment administration into the pleural space. This study aims at exploring CD146 as a potential MPM cell-specific target for engineered Pe-loaded GNPs and to assess their effectiveness in inhibiting MPM cell line growth.MethodsMPM cell lines and primary cultures obtained by pleural effusions from MPM patients were assayed for CD146 expression by flow cytometry. Internalization by MPM cell lines of fluorescent dye-marked GNPs decorated with a monoclonal anti CD146 coated GNPs (GNP-HC) was proven by confocal microscopy. The effects of anti CD146 coated GNPs loaded with Pe (GNP-HCPe) on MPM cell lines were evaluated by cell cycle (flow cytometry), viability (MTT test), clonogenic capacity (soft agar assay), ROS production (electric paramagnetic resonance), motility (wound healing assay), and apoptosis (flow cytometry).ResultsGNP-HC were selectively uptaken by MPM cells within 1 hour. MPM cell lines were blocked in the S cell cycle phase in the presence of GNP-HCPe. Both cell viability and motility were significantly affected by nanoparticle treatment compared to Pe. Apoptotic rate and ROS production were significantly higher in the presence of nanoparticles. Clonogenic capacity was completely inhibited following nanoparticle internalization.ConclusionGNP-HCPe treatment displays in vitro antineoplastic action and is more effective than Pe alone in inhibiting MPM cell line malignant phenotype. The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy.

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Section: Discussionsupporting

confidence: 77%

<p>Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study</p>

Cova

Pandolfi

Colombo

et al. 2019

IJN

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“…The up-regulation of CD146 in cells associated with regenerating blood vessels in the nerve bridge and the network analysis results indicate that CD146 could take part blood vessel regeneration in the nerve bridge by interacting with VEGF and FGF2 signaling pathways (Figure 6). In line with this finding, CD146 has a well characterized function in promoting angiogenesis and vascular development (St Croix, 2015;Tu et al, 2015). The other biological function for CD146 is to regulate cell migration (Figure 6).…”

Section: Identifying Interaction Network Of Cd146supporting

confidence: 70%

“…Later studies have demonstrated that CD146 is highly expressed on a variety of carcinomas in addition to melanoma, and therefore CD146 has been suggested as a potential marker for tumor diagnosis, prognosis and treatment ( Wang and Yan, 2013 ). However, recent reports have shown that CD146 not only just acts as a cell adhesion molecule to mediate cell-cell interaction and cell-matrix adhesion, it also acts as a cell surface receptor to transduce extracellular signals ( St Croix, 2015 ; Tu et al, 2015 ). It is actively involved in many physiological processes such as organ development, cell migration, angiogenesis, immune response and tissue repair ( St Croix, 2015 ; Tu et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Up-Regulation of CD146 in Schwann Cells Following Peripheral Nerve Injury Modulates Schwann Cell Function in Regeneration

Shen

Jun

Liu

et al. 2021

Front. Cell. Neurosci.

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CD146 is cell adhesion molecule and is implicated in a variety of physiological and pathological processes. However, the involvement of CD146 in peripheral nerve regeneration has not been studied yet. Here, we examine the spatial and temporal expression pattern of CD146 in injured mouse sciatic nerve via high-throughput data analysis, RT-PCR and immunostaining. By microarray data analysis and RT-PCR validation, we show that CD146 mRNA is significantly up-regulated in the nerve bridge and in the distal nerve stump following mouse sciatic nerve transection injury. By single cell sequencing data analysis and immunostaining, we demonstrate that CD146 is up-regulated in Schwann cells and cells associated with blood vessels following mouse peripheral nerve injury. Bioinformatic analysis revealed that CD146 not only has a key role in promoting of blood vessel regeneration but also regulates cell migration. The biological function of CD146 in Schwann cells was further investigated by knockdown of CD146 in rat primary Schwann cells. Functional assessments showed that knockdown of CD146 decreases viability and proliferation of Schwann cells but increases Schwann cell migration. Collectively, our findings imply that CD146 could be a key cell adhesion molecule that is up-regulated in injured peripheral nerves to regulate peripheral nerve regeneration.

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“…As we find that BRB treatment from 72 hpf causes an increased and abnormal angiogenesis in both ISVs and SIV during embryonic development, we hypothesize that discrepancies between our results and those previously reported may be due, at least in part, to the different experimental protocol used, BRB concentration, formulation and administration time. In this respect, some compounds may exert pro-or anti-angiogenic effects depending on their concentration 55 or on the developmental stage of treated embryos/fetuses 24,27 . Additionally, since an aberrant vascularization may be involved in the genesis of pericardial edema in vertebrates 39,49 , we hypothesize that the altered angiogenesis we observed may also play a role in the pericardial edema formation in BRB-treated developing embryos.…”

Section: Discussionmentioning

confidence: 99%

Exposure to the natural alkaloid Berberine affects cardiovascular system morphogenesis and functionality during zebrafish development

Martini

Pucci

Gabellini

et al. 2020

Sci Rep

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The plant-derived natural alkaloid berberine displays therapeutic potential to treat several pathological conditions, including dyslipidemias, diabetes and cardiovascular disorders. However, data on berberine effects during embryonic development are scarce and in part controversial. In this study, using zebrafish embryos as vertebrate experimental model, we address the effects of berberine treatment on cardiovascular system development and functionality. Starting from the observation that berberine induces developmental toxicity and pericardial edema in a time- and concentration-dependent manner, we found that treated embryos display cardiac looping defects and, at later stages, present an abnormal heart characterized by a stretched morphology and atrial endocardial/myocardial detachment. Furthermore, berberine affected cardiac functionality of the embryos, promoting bradycardia and reducing the cardiac output, the atrial shortening fraction percentage and the atrial stroke volume. We also found that, during development, berberine interferes with the angiogenic process, without altering vascular permeability. These alterations are associated with increased levels of vascular endothelial growth factor aa (vegfaa) mRNA, suggesting an important role for Vegfaa as mediator of berberine-induced cardiovascular defects. Altogether, these data indicate that berberine treatment during vertebrate development leads to an impairment of cardiovascular system morphogenesis and functionality, suggesting a note of caution in its use during pregnancy and lactation.

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CD146: the unveiling of a pro-angiogenic netrin receptor

Cited by 9 publications

References 12 publications

<p>Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study</p>

<p>Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study</p>

Up-Regulation of CD146 in Schwann Cells Following Peripheral Nerve Injury Modulates Schwann Cell Function in Regeneration

Exposure to the natural alkaloid Berberine affects cardiovascular system morphogenesis and functionality during zebrafish development

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