scholarly journals Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patrick Meylan ◽  
Christine Pich ◽  
Carine Winkler ◽  
Stefanie Ginster ◽  
Lionel Mury ◽  
...  
Keyword(s):  
Melanoma Cell ◽  
Tumor Regression ◽  
Lung Metastases ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Human Melanoma Cell ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Thioredoxin System

AbstractThe thioredoxin system plays key roles in regulating cancer cell malignancy. Here we identify the Thioredoxin-interacting protein (TXNIP) as a gene, which expression is regulated by PPARγ in melanoma cells. We show that high TXNIP expression levels associate with benign melanocytic lesions, with tumor regression in patients on MAP kinase targeted therapy, with decreased proliferation in patients’ melanoma biopsies, and with cell cycle arrest in human melanoma cell lines. In contrast, reduced TXNIP expression associates with advanced melanoma and with disease progression in patients. TXNIP depletion in human melanoma cells altered the expression of integrin beta-3 and the localization of the integrin alpha-v/beta-3 dimer at their surface. Moreover, TXNIP depletion affected human melanoma cell motility and improved their capacity to colonize mouse lungs in an in vivo assay. This study establishes TXNIP as a PPARγ-regulated gene in melanoma cells, thereby suggesting a link between these two proteins both involved in the regulation of cancer and of energy metabolism. It also reveals that the decrease in TXNIP expression, which is observed in advanced patient tumors, likely favors lung metastatic seeding of malignant cells.

scholarly journals Nck2 promotes human melanoma cell proliferation, migration and invasion in vitro and primary melanoma-derived tumor growth in vivo

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Mélissa Labelle-Côté ◽  
Julie Dusseault ◽  
Salma Ismaïl ◽  
Aude Picard-Cloutier ◽  
Peter M Siegel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Melanoma Cell ◽  
Primary Melanoma ◽  
Human Melanoma ◽  
Human Melanoma Cell ◽  
Migration And Invasion ◽  
Melanoma Cell Proliferation

A monoclonal antibody (LYP18) directed against the blood platelet glycoprotein IIb/IIIa complex inhibits human melanoma growth in vivo

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 909-912
Author(s):  
H Boukerche ◽  
O Berthier-Vergnes ◽  
M Bailly ◽  
JF Dore ◽  
LL Leung ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Melanoma Cell ◽  
Blood Platelet ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Platelet Glycoprotein ◽  
Novel Approach ◽  
Growth Of Tumor

A monoclonal antibody (MoAb) (LYP18), generated against human platelet glycoprotein IIb/IIIa (GPIIb/IIIa), immuno-precipitated a IIb/IIIa-like GP complex from a highly tumorigenic human melanoma cell line (M3Dau). The M3Dau melanoma cells specifically bound 125I-labeled LYP18. To study the biologic role of these IIb/IIIa-like glycoproteins, M3Dau melanoma cells were incubated with LYP18 or a control MoAb directed against another melanoma cell-surface antigen and implanted subcutaneously (SC) in nude mice. LYP18 dramatically inhibited the growth of tumor in vivo. LYP18 was not directly cytotoxic to the melanoma cells. These results demonstrate that the IIb/IIIa-like GPs are present on melanoma cells and play a crucial role in tumor cell growth. MoAbs directed against tumor cytoadhesive receptors may represent a novel approach in tumor treatment.

Effect of small inhibitors of nuclear export (SINE) on growth inhibition and apoptosis of human melanoma cells.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13549-e13549
Author(s):  
Gregory B. Lesinski ◽  
Jennifer Yang ◽  
Matthew A Bill ◽  
Yosef Landesman ◽  
Sharon Shacham ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Nuclear Export ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Human Melanoma Cell ◽  
Nuclear Accumulation ◽  
Dependent Manner ◽  
Melanoma Cell Lines

e13549 Background: Inhibition of nuclear export can promote re-activation of tumor suppressor pathways. CRM1 (chromosomal regional maintenance 1) or XPO1 (exportin 1) is the major protein that mediates nuclear export. We hypothesized that CRM1 mediated nuclear export represents a novel therapeutic target that can be manipulated to inhibit melanoma cell survival. Methods: The growth inhibitory and pro-apoptotic effects of KPT-185, KPT-276 and KPT-330, small molecules selective inhibitor of nuclear export (SINE) were evaluated in human melanoma cell lines using an MTT assay and Annexin V/PI staining, respectively. Fluorescence microscopy and immunoblots were used to assess nuclear accumulation of tumor suppressor proteins. The trans-isomer of KPT-185 and DMSO (vehicle) were used as a negative controls in all assays. The pharmacokinetic (PK) profile of all compounds was evaluated in mice. Results: CRM1 protein was highly expressed in human melanoma cell lines with diverse molecular profiles (i.e., B-Raf, NRAS, p53). KPT-SINE inhibited melanoma cell growth in a concentration-dependent manner and induced apoptosis at nanomolar concentrations. Importantly, there was no evidence that B-Raf V600 mutational status influenced melanoma cell response to these agents. Nuclear accumulation and/or induction of p53, p21, FOXO3a, STAT1 and BAD, and reduction of MCL-1 occurred in melanoma cells at time points prior to apoptosis as shown by increase in cleaved PARP and caspase 3 levels. PK studies were conducted in mice following oral administration of 10 mg/kg, to guide drug selection for our ongoing efficacy studies in murine melanoma models. KPT-185 showed limited bioavailability and systemic exposure, while KPT-276 and KPT-330 showed >50% bioavailability reaching Cmax >5µM. Conclusions: This study represents the first report of CRM1 inhibition in melanoma. These data indicate that the novel SINE compounds can effectively inhibit CRM1-mediated nuclear export and induce apoptosis in melanoma cells. KPT-330 is currently under development as orally bioavailable, small molecule inhibitors for a human clinical trial.

Luteolin inhibits proliferation and induces apoptosis of human melanoma cells in vivo and in vitro by suppressing MMP-2 and MMP-9 through the PI3K/AKT pathway

2019 ◽  
Vol 10 (2) ◽  
pp. 703-712 ◽  
Author(s):  
Xin Yao ◽  
Wei Jiang ◽  
Danhong Yu ◽  
Zhaowei Yan
Keyword(s):  
Malignant Melanoma ◽  
Incidence Rate ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Akt Pathway ◽  
Human Melanoma Cells ◽  
Cell Metastasis

Since the incidence rate of malignant melanoma is increasing annually, development of drugs against melanoma cell metastasis has become more urgent.

scholarly journals SUN-LB27 Interleukin-8 - a Possible Target for Melanoma Treatment? In-Vitro Studies Based on Human Melanoma Cell Models

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Pandurangan Ramaraj
Keyword(s):  
Cell Growth ◽  
Melanoma Cell ◽  
In Vitro Study ◽  
Human Melanoma ◽  
Human Melanoma Cell ◽  
Melanoma Treatment ◽  
Pre Treatment ◽  
Melanoma Growth

Abstract Previous clinical studies showed that menstruating females were better protected in melanoma than post-menopausal women and men of any age. In addition, epidemiological studies showed an increased male mortality in melanoma. But these studies did not correlate with steroid status in females. Our in-vitro study showed female sex hormone progesterone significantly inhibited human melanoma cell growth. Further in-vitro study showed that progesterone action was mediated by a specific suppression of pro-inflammatory cytokine IL-8. Our research also showed that addition of IL-8 (1 ng/ml) to melanoma cells stimulated cell growth (117%) and suppression of IL-8 by curcumin (100 μM) pre-treatment suppressed human melanoma cell growth (26%) in-vitro. This observation prompted us to check the effect of male sex hormones androstenedione (AD) and testosterone (T) on melanoma cell growth. AD and T also suppressed cell growth and IL-8 secretion, but not as significantly as that of progesterone. However, addition of progesterone (10 μM) along with androgens showed an additive effect on the inhibition of melanoma cell growth and suppression of IL-8 secretion. As steroids (P, AD, T) targeted IL-8 for their action, it was decided to check whether vitamin-D3 also targeted IL-8 secretion and cell growth. Active form of vit-D3 (25 μM) also suppressed IL-8 secretion and cell growth. But, addition of progesterone (50 μM) along with D3 significantly suppressed cell growth and IL-8 secretion. This brought IL-8 into focus as a key molecule regulating melanoma cell growth. In order to check whether IL-8 was the molecule involved in regulating melanoma cell growth, IL-8 rescue experiment after curcumin (25 μM) pre-treatment was carried out. IL-8 (100 ng/ml) was able to rescue cell growth completely after pre-treatment with curcumin, suggesting IL-8 was the molecule involved in regulating melanoma cell growth. Literature also suggested important role for IL-8 in regulating melanoma cell growth. Conditional expression of IL-8 in nude mouse by Dr. Singh et al., indicated in-vivo role of IL-8 in melanoma growth and metastasis. Conclusion: Both, in-vitro and in-vivo studies suggested an important role for IL-8 in regulating melanoma growth and metastasis. So, IL-8 could be targeted to arrest melanoma growth and metastasis in-vivo. Hence, IL-8 could be a potential target for melanoma treatment.

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