Endothelial Cells Require CD98 for Efficient Angiogenesis—Brief Report

Liao, Zhongji; Cantor, Joseph M.

doi:10.1161/atvbaha.116.308335

Cited by 13 publications

(12 citation statements)

References 18 publications

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“…In this regard, it has been shown that over-expression of SLC3A2 is actively involved in the proliferation of vascular smooth muscle cells and is necessary for efficient angiogenesis. 38, 39 In this study, ER+ high-proliferation and TN tumours showed the most significant positive correlation between the mRNA expression of SLC3A2 and vascular endothelial growth factor B, which maintains the continuity of angiogenesis and thus implicated for the metastatic process. 40 Although the association between HER2+ tumours and patient outcome was not nominally significant, there was no difference in the effect of this subtype and the other aggressive tumour types.…”

Section: Discussionmentioning

confidence: 50%

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

et al. 2018

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Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity and patient outcome. This study aimed to evaluate the biological and prognostic value of the membrane solute carrier, SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. SLC3A2 was assessed at the genomic level, using METABRIC data (n = 1980), and at the proteomic level, using immunohistochemistry on tissue microarray (TMA) sections constructed from a large well-characterised primary BC cohort (n = 2500). SLC3A2 expression was correlated with clinicopathological parameters, molecular subtypes and patient outcome. SLC3A2 mRNA and protein expression were strongly correlated with higher tumour grade and poor Nottingham prognostic index (NPI). High expression of SLC3A2 was observed in triple-negative (TN), HER2+ and ER+ high-proliferation subtypes. SLC3A2 mRNA and protein expression were significantly associated with the expression of c-MYC in all BC subtypes (p < 0.001). High expression of SLC3A2 protein was associated with poor patient outcome (p < 0.001), but only in the ER+ high-proliferation (p = 0.01) and TN (p = 0.04) subtypes. In multivariate analysis SLC3A2 protein was an independent risk factor for shorter BC-specific survival (p < 0.001). SLC3A2 appears to play a role in the aggressive BC subtypes driven by MYC and could act as a potential prognostic marker. Functional assessment is necessary to reveal its potential therapeutic value in the different BC subtypes.

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Section: Discussionmentioning

confidence: 50%

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

et al. 2018

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“…Focused study of the mechanisms of vascular development can produce surprising clues about adult vascular disease as cells respond to tissue damage and reexpress developmental programs to repair injury and remodel vessel walls. 101–106…”

Section: Discussionmentioning

confidence: 99%

Vascular Development

Majesky

2018

ATVB

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The vascular system forms as a branching network of endothelial cells that acquire identity as arterial, venous, hemogenic, or lymphatic. Endothelial specification depends on gene targets transcribed by Ets domain-containing factors, including Ets variant gene 2 (Etv2), together with the activity of chromatin remodeling complexes containing Brahma-related gene-1 (Brg1). Once specified and assembled into vessels, mechanisms regulating lumen diameter and axial growth ensure that the structure of the branching vascular network matches the need for perfusion of target tissues. In addition, blood vessels provide important morphogenic cues that guide or direct the development of organs forming around them. As the embryo grows and lumen diameters increase, smooth muscle cells (SMCs) wrap around the nascent vessel walls to provide mechanical strength and vasomotor control of the circulation. Increasing mechanical stretch and wall strain promote SMC differentiation via coupling of actin cytoskeletal remodeling to myocardin and serum response factor-dependent transcription. Remodeling of artery walls by developmental signaling pathways reappears in postnatal blood vessels during physiological and pathological adaptation to vessel wall injury, inflammation or chronic hypoxia. Recent reports providing insights into major steps in vascular development are reviewed here with a particular emphasis on studies that have been recently published in Arteriosclerosis, Thrombosis, and Vascular Biology.

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“…Additionally, CD98 expression is implicated in increased vascular density (Supplemental Figs. 2A and 2B, bottom) (26). The correlation between vascular density and LAT1 expression is corroborated by preclinical 11 C-methionine PET studies on gliomas and brain tumors (27 Data are mean correlation coefficient followed by 5%-95% confidence interval in parentheses.…”

Section: Discussionmentioning

confidence: 77%

Imaging Melphalan Therapy Response in Preclinical Extramedullary Multiple Myeloma with ¹⁸F-FDOPA and ¹⁸F-FDG PET

et al. 2018

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Multiple myeloma (MM) is a debilitating neoplasm of terminally differentiated plasma B cells that resulted in over 13,000 deaths in 2017 alone. Combination therapies involving melphalan, a small-molecule DNA alkylating agent, are commonly prescribed to patients with relapsed or refractory MM, necessitating the stratification of responding patients to minimize toxicities and improve quality of life. Here, we evaluated the use of 3,4-dihydroxy-6-F-fluoro-l-phenylalanine (F-FDOPA), a clinically available PET radiotracer with specificity to the L-type amino acid transporter 1 (LAT1), which also mediates melphalan uptake, for imaging melphalan therapy response in a preclinical immunocompetent model of MM. C57BL/KaLwRij mice were implanted subcutaneously with unilateral murine green fluorescent protein-expressing 5TGM1 tumors and divided into 3 independent groups: untreated, treated beginning week 2 after tumor implantation, and treated beginning week 3 after tumor implantation. The untreated and week 2 treated groups were imaged with preclinical MRI and dynamicF-FDG and F-FDOPA PET/CT at week 4 on separate, contiguous days, whereas the week 3 treated group was longitudinally imaged weekly for 3 wk. Metabolic tumor volume, total lesion avidity, SUV, and total uptake were calculated for both tracers. Immunohistochemistry was performed on representative tissue from all groups for LAT1 and glucose transporter 1 (GLUT1) expression. Melphalan therapy induced a statistically significant reduction in lesion avidity and uptake for bothF-FDG and F-FDOPA. There was no visible effect on GLUT1 expression, but LAT1 density increased in the week 2 treated group. Longitudinal imaging of the week 3 treated group showed variable changes inF-FDG and F-FDOPA uptake, with an increase inF-FDOPA lesion avidity in the second week relative to baseline. LAT1 and GLUT1 surface density in the untreated and week 3 treated groups were qualitatively similar. F-FDOPA PET/CT complementedF-FDG PET/CT in imaging melphalan therapy response in preclinical extramedullary MM. F-FDOPA uptake was linked to LAT1 expression and melphalan response, with longitudinal imaging suggesting stabilization of LAT1 levels and melphalan tumor cytotoxicity. Future work will explore additional MM cell lines with heterogeneous LAT1 expression and response to melphalan therapy.

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Endothelial Cells Require CD98 for Efficient Angiogenesis—Brief Report

Cited by 13 publications

References 18 publications

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

Vascular Development

Imaging Melphalan Therapy Response in Preclinical Extramedullary Multiple Myeloma with ¹⁸F-FDOPA and ¹⁸F-FDG PET

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Endothelial Cells Require CD98 for Efficient Angiogenesis—Brief Report

Cited by 13 publications

References 18 publications

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

Vascular Development

Imaging Melphalan Therapy Response in Preclinical Extramedullary Multiple Myeloma with 18F-FDOPA and 18F-FDG PET

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Product

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Imaging Melphalan Therapy Response in Preclinical Extramedullary Multiple Myeloma with ¹⁸F-FDOPA and ¹⁸F-FDG PET