Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1658953 (tumor vasculature)
 2,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histologic cell type, largest tumor diameter and tumor location have traditionally been regarded as the leading predictors of survival for uveal melanoma. Morphological cell typing is, however, subjective to variations in interpretation. More objective classification parameters have emerged from extensive cytomorphometrical and DNA flow cytometrical studies. For patients with uveal melanoma there is no effective therapy if metastases have developed, and the median survival after clinical diagnosis of hepatic metastases is extremely poor. Current research focuses on the mechanisms underlying the metastatic process, including tumor vasculature, cytogenetics, oncogene activation, immunology, melanoma-associated antigens and tumor cell migration (cell-cell and cell-matrix interaction). Several new prognostic parameters have emerged from these studies, such as closed vascular patterns, loss of one chromosome 3, and different indices of cell proliferation. Furthermore, considerable genotypical and phenotypical differences have been found between uveal and cutaneous melanoma. In prospective studies on large series of melanomas a combination of histopathological and/or clinical prognostic parameters might be selected with high sensitivity and specificity, providing a way of selecting patients at high risk of developing metastatic disease, who might be eligible for adjuvant therapy.
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PMID:Prognostic parameters in uveal melanoma: a review. 897 Feb 36

Tumors are complex tissues composed of neoplastic cells, soluble and insoluble matrix components and stromal cells. Here we report that in melanoma, turn-over of type I collagen (Col(I)), the predominant matrix protein in dermal stroma affects melanoma progression. Fibroblasts juxtaposed to melanoma cell nests within the papillary dermis display high levels of Col(I) mRNA expression. These nests are enveloped by collagen fibers. In contrast, melanoma-associated fibroblasts within the reticular dermis express Col(I) mRNA at a level that is comparable to its expression in uninvolved dermis and reduced amount of collagen protein can be observed. To determine the significance of Col(I) expression in melanoma, we pharmacologically inhibited its transcription in a porcine cutaneous melanoma model by oral administration of halofuginone. When administered before melanoma development, it reduced melanoma incidence and diminished the transition from microinvasive toward deeply invasive growth by limiting the development of a tumor vasculature. Whereas invasive melanoma growth has been correlated with increased blood vessel density previously, our data for the first time demonstrate that the proangiogenic effect of Col(I) expression by fibroblasts and vascular cells precedes the development of invasive melanomas in a de novo tumor model.
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PMID:Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma. 1795 94

A progressive increase in copy number variation (CNV) characterizes the natural history of cutaneous melanoma progression toward later disease stages, but our understanding of genetic drivers underlying chromosomal arm-level CNVs remains limited. To identify candidate progression drivers, we mined the TCGA SKCM dataset and identified HDGF as a recurrently amplified gene whose high mRNA expression correlates with poor patient survival. Using melanocyte-specific overexpression in the zebrafish BRAFV600E -driven MiniCoopR melanoma model, we show that HDGF accelerates melanoma development in vivo. Transcriptional analysis of HDGF compared to control EGFP tumors showed the activation of endothelial/angiogenic pathways. We validated this observation using an endothelial kdrl:mCherry reporter line which showed HDGF to increases tumor vasculature. HDGF is frequently co-altered with the established melanoma driver SETDB1. Both genes are located on chromosome 1q, and their co-amplification is observed in up to 13% of metastatic melanoma. TCGA patients with both genes amplified and/or overexpressed have a worse melanoma specific survival. We tested co-expression of HDGF and SETDB1 in the MiniCoopR model, which resulted in faster and more aggressive melanoma development than either gene individually. Our work identifies the co-amplification of HDGF and SETDB1 as a functional driver of melanoma progression and poor patient prognosis.
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PMID:Recurrent co-alteration of HDGF and SETDB1 on chromosome 1q drives cutaneous melanoma progression and poor prognosis. 3306 82