Increased HIF-1α Expression Correlates With Cell Proliferation and Vascular Markers CD31 and VEGF-A in Uveal Melanoma

Mouriaux, Frédéric; Sanschagrin, François; Diorio, Caroline; Landreville, Solange; Comoz, F.; Petit, Edwige; Bernaudin, Myriam; Rousseau, A.; Bergeron, Dan; Morcos, Mohib

doi:10.1167/iovs.13-13345

Cited by 37 publications

(25 citation statements)

References 55 publications

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“…Differences in angiogenesis could explain the observed correlation of K trans and monosomy 3. Vascular endothelial growth factor and hypoxia-inducible factor 1α have both been detected in uveal melanoma; however, conflicting data exist regarding the relationship between their expression levels, rate of metastasis, and patient survival [18][19][20]. Furthermore, neither VEGF nor HIF-1α levels have been definitely correlated with monosomy 3 status.…”

Section: Discussionmentioning

confidence: 99%

Quantitative multiparametric MRI in uveal melanoma: increased tumor permeability may predict monosomy 3

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Quantitative multiparametric MRI in uveal melanoma: increased tumor permeability may predict monosomy 3

et al. 2015

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“…LOX has also been linked to HIF-driven metastasis in multiple different tumor types and it is believed to promote metastasis by remodelling the extracellular matrix [22]–[24]. Recently, the increased expression of HIF-1α has been shown to be significantly associated with proliferative (MIB-1) and vascular (CD31 and VEGF-A) markers in uveal melanoma primary tumors, even though no significant correlation was observed between HIF-1α expression and patient survival [25].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Promotes Uveal Melanoma Invasion through Enhanced Notch and MAPK Activation

et al. 2014

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The transcriptional response promoted by hypoxia-inducible factors has been associated with metastatic spread of uveal melanoma. We found expression of hypoxia-inducible factor 1α (HIF-1α) protein in well-vascularized tumor regions as well as in four cell lines grown in normoxia, thus this pathway may be important even in well-oxygenated uveal melanoma cells. HIF-1α protein accumulation in normoxia was inhibited by rapamycin. As expected, hypoxia (1% pO2) further induced HIF-1α protein levels along with its target genes VEGF and LOX. Growth in hypoxia significantly increased cellular invasion of all 5 uveal melanoma lines tested, as did the introduction of an oxygen-insensitive HIF-1α mutant into Mel285 cells with low HIF-1α baseline levels. In contrast, HIF-1α knockdown using shRNA significantly decreased growth in hypoxia, and reduced by more than 50% tumor invasion in four lines with high HIF-1α baseline levels. Pharmacologic blockade of HIF-1α protein expression using digoxin dramatically suppressed cellular invasion both in normoxia and in hypoxia. We found that Notch pathway components, including Jag1-2 ligands, Hes1-Hey1 targets and the intracellular domain of Notch1, were increased in hypoxia, as well as the phosphorylation levels of Erk1-2 and Akt. Pharmacologic and genetic inhibition of Notch largely blocked the hypoxic induction of invasion as did the pharmacologic suppression of Erk1-2 activity. In addition, the increase in Erk1-2 and Akt phosphorylation by hypoxia was partially reduced by inhibiting Notch signaling. Our findings support the functional importance of HIF-1α signaling in promoting the invasive capacity of uveal melanoma cells in both hypoxia and normoxia, and suggest that pharmacologically targeting HIF-1α pathway directly or through blockade of Notch or Erk1-2 pathways can slow tumor spread.

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“…Therefore, HIF (HIF1, in particular) plays a major role in tumor growth, and clinical data suggest that the upregulation of HIF, as determined by the low oxygen tension, is usually associated with increased mortality in a number of different cancers [92][93][94], and may represent a relevant target for new therapeutic approaches to the disease [95][96][97].…”

Section: Myeloid Leukemiamentioning

confidence: 99%

High Doses of Vitamin C and Leukemia: In Vitro Update

Milardi¹,

Massai²,

Fioritoni³

et al. 2018

Myeloid Leukemia

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Vitamin C (ascorbic acid) is an essential nutrient with a number of beneficial effects on the human body. Although the majority of mammals can synthesize their own Vitamin C, humans and a few other species, do not produce it and depend on dietary sources for their Vitamin C supply. Among its many effects on cell function and metabolism, Vitamin C has shown, in vitro, a powerful anticancer effect against a number of human tumor cell lines, including myeloid leukemia. There are many different mechanistic explanations for the anticancer/anti-leukemic effects of Vitamin C and the aim of the present review is to illustrate these mechanisms, showing the results of some preliminary in vitro investigations, and outlining their potential clinical relevance.

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Increased HIF-1α Expression Correlates With Cell Proliferation and Vascular Markers CD31 and VEGF-A in Uveal Melanoma

Abstract: An increase in HIF-1α expression was significantly associated with proliferative (MIB-1) and vascular (CD31 and VEGF-A) markers, as well as necrosis, in UM. However, there was no correlation between high HIF-1α expression and patient survival.

Cited by 37 publications

References 55 publications

Quantitative multiparametric MRI in uveal melanoma: increased tumor permeability may predict monosomy 3

Quantitative multiparametric MRI in uveal melanoma: increased tumor permeability may predict monosomy 3

Hypoxia Promotes Uveal Melanoma Invasion through Enhanced Notch and MAPK Activation

High Doses of Vitamin C and Leukemia: In Vitro Update

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