Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Hyal-1 locus, which we have previously described and mapped to mouse chromosome 9, influences the serum levels and molecular weight forms of hyaluronidase. We have also shown that the growth of two transplantable tumors, the 3LL carcinoma and the B16F10 melanoma, is influenced by the alleles at Hyal-1, in that the tumors develop more slowly in congenic B6.C-Hyal-1a (also called HW23) mice than in the parental Hyal-1b C57BL/6 mice. Here we present evidence that tumor development is stimulated and mortality is accelerated in B6.C-Hyal-1a mice grafted with 3LL carcinoma cells when treated with alpha/beta interferon (IFN-alpha/beta) or with IFN-beta, whereas in IFN-treated C57BL/6 mice 3LL tumor growth is inhibited. Likewise, in B6.C-Hyal-1a mice grafted with B16F10 melanoma cells, IFN-alpha/beta treatment results in stimulation of tumor growth, whereas in IFN-treated C57BL/6 mice tumor growth, whereas in IFN-treated C57BL/6 mice tumor growth is inhibited and mortality delayed. Thus, IFN-alpha/beta treatment of B6.C-Hyal-1a mice results in stimulation of tumor development and sometimes in accelerated mortality. This is the opposite of the usually described effect of IFN treatment in mice, which is inhibition of tumor development and delayed mortality, as was indeed observed in the C57BL/6 mice in the present experiments. These results provide the first indication that host genes can up- or down-regulate the antitumor activity of IFN and that, on some genetic backgrounds, IFN treatment enhances rather than inhibits tumor development. This may help to explain the apparent discordance between mouse model studies, which hitherto have consistently reported inhibition of tumor formation by IFN, and the clinical trials, in which only a limited percentage of individuals show tumor regression while others have no beneficial effect or even have progression of disease in spite of the IFN treatment.
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PMID:Accelerated tumor development in interferon-treated B6.C-Hyal-1 a mice. 851 20

Hyaluronan is a negatively charged, high molecular weight glycosaminoglycan found predominantly in the extracellular matrix. Intracellular locations for hyaluronan have also been documented in cytoplasm, nucleus, and nucleolus. The polymer has an extraordinarily high rate of turnover in vertebrate tissues. The focus here is to formulate a metabolic pathway for hyaluronan degradation using all available data, including the recently acquired information on the hyaluronidase gene family. Such a catabolic scheme has defied explication up to now. In somatic tissues, stepwise processing occurs, from the extracellular high molecular weight space filling, antiangiogenic approximately 107-kDa polymer, to intermediate sized highly angiogenic, inflammatory, and immune-stimulating fragments, and ultimately to tetrasaccharides that are antiapoptotic and potent inducers of heat-shock proteins. It is proposed that the high molecular weight extracellular polymer is tethered to the cell surface by the combined efforts of hyaluronan receptors and hyaluronidase-2 (Hyal-2). The hyaluronan is cleaved to a 20-kDa intermediate-sized fragment, the limit product of Hyal-2 digestion. These fragments are delivered to endosomal- and ultimately lysosomal-like structures. Further catabolism occurs there by Hyal-1, coordinated with the activity of two lysosomal beta-exoglycosidases, beta-glucuronidase and beta-N-acetyl-glucosaminidase. A membrane-associated mini-organelle is postulated, the hyaluronasome, in which coordinated synthetic and catabolic enzyme reactions occur. The hyaluronasome can respond to the physiological states of the cell by a series of membrane-bound and soluble hyaluronan-associated receptors, binding proteins, and cofactors that trigger enzymatic events and signal transduction pathways. These in turn can be modulated by the amounts and sizes of the hyaluronan polysaccharides generated in the catabolic cascade. Most of these highly dynamic interactions remain to be determined. It is also proposed that malignant cells can commandeer some of these interactions for facilitating tumor growth and spread.
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PMID:Devising a pathway for hyaluronan catabolism: are we there yet? 1451 8

Tumor cells express HYAL1 hyaluronidase, which degrades hyaluronic acid. HYAL1 expression in bladder cancer cells promotes tumor growth, invasion, and angiogenesis. We previously described five alternatively spliced variants of HYAL1 that encode enzymatically inactive proteins. The HYAL1-v1 variant lacks a 30-amino acid sequence that is present in HYAL1. In this study, we examined whether HYAL1-v1 expression affects bladder cancer growth and invasion by stably transfecting HT1376 bladder cancer cells with a HYAL1-v1 cDNA construct. Although HYAL1-v1 transfectants expressed equivalent levels of enzymatically active HYAL1 protein when compared with vector transfectants, their conditioned medium had 4-fold less hyaluronidase activity due to a noncovalent complex formed between HYAL1 and HYAL1-v1 proteins. HYAL1-v1 transfectants grew 3- to 4-fold slower due to cell cycle arrest in the G(2)-M phase and increased apoptosis. In HYAL1-v1 transfectants, cyclin B1, cdc2/p34, and cdc25c levels were > or =2-fold lower than those in vector transfectants. The increased apoptosis in HYAL1-v1 transfectants was due to the extrinsic pathway involving Fas and Fas-associated death domain up-regulation, caspase-8 activation, and BID cleavage, leading to caspase-9 and caspase-3 activation and poly(ADP-ribose) polymerase cleavage. When implanted in athymic mice, HYAL1-v1-expressing tumors grew 3- to 4-fold slower and tumor weights at day 35 were 3- to 6-fold less than the vector tumors (P < 0.001). Whereas vector tumors were infiltrating and had high mitoses and microvessel density, HYAL1-v1 tumors were necrotic, infiltrated with neutrophils, and showed low mitoses and microvessel density. Therefore, HYAL-v1 expression may negatively regulate bladder tumor growth, infiltration, and angiogenesis.
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PMID:HYAL1-v1, an alternatively spliced variant of HYAL1 hyaluronidase: a negative regulator of bladder cancer. 1714 67

Extracellular matrix (ECM) is closely correlated with tumor cell growth, proliferation, metastasis and angiogenesis, etc. Hyaluronic acid (HA) is a component of the ECM, and hyaluronidase (HAase) is a HA-degrading endoglycosidase. Levels of HAase are elevated in many cancers. Hyaluronidase-1 (HYAL1) is the major tumor-derived HAase. In this study, we detected HYAL1 expression levels in breast cancer cells and tissues, and measured the amount HAase activity in breast cancer cells. Compared with nonmalignant breast cell line HBL-100 and normal breast tissues, HYAL1 were overexpressed in breast cancer cell lines MDA-MB-231, MCF-7, invasive duct cancer tissues and metastatic lymph nodes, respectively. Accordingly, the amount HAase activity in MDA-MB-231 and MCF-7 was higher than that in HBL-100. In addition, knockdown of HYAL1 expression in MDA-MB-231 and MCF-7 cells resulted in decreased cell growth, adhesion, invasion and angiogenesis potential. Meantime, the HYAL1 knockdown markedly inhibited breast cancer cell xenograft tumor growth and microvessel density. Further studies showed that the HYAL1, HYAL2 and HA were elevated in breast cancer, and HYAL1 could downregulate HA expression. In conclusion, HYAL1 may be a potential prognostic marker and therapeutic target in breast cancer.
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PMID:HYAL1 overexpression is correlated with the malignant behavior of human breast cancer. 2047 47

Hyaluronic acid (HA) is a component of the Extra-cellular matrix (ECM), it is closely correlated with tumor cell growth, proliferation, metastasis and angiogenesis, etc. Hyaluronidase (HAase) is a HA-degrading endoglycosidase, levels of HAase are elevated in many cancers. Hyaluronidase-1 (HYAL1) is the major tumor-derived HAase. We previously demonstrated that HYAL1 were overexpression in human breast cancer. Breast cancer cells with higher HAase expression, exhibited significantly higher invasion ability through matrigel than those cells with lower HAase expression, and knockdown of HYAL1 expression in breast cancer cells resulted in decreased cell growth, adhesion, invasion and angiogenesis. Here, to further elucidate the function of HYAL1 in breast cancer, we investigated the consequences of forcing HYAL1 expression in breast cancer cells by transfection of expression plasmid. Compared with control, HYAL1 up-regulated cells showed increased the HAase activity, and reduced the expression of HA in vitro. Meantime, upregulation of HYAL1 promoted the cell growth, migration, invasion and angiogenesis in vitro. Moreover, in nude mice model, forcing HYAL1 expression induced breast cancer cell xenograft tumor growth and angiogenesis. Interestingly, the HA expression was upregulated by forcing HYAL1 expression in vivo. These findings suggested that HYAL1-HA system is correlated with the malignant behavior of breast cancer.
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PMID:Upregulation of HYAL1 expression in breast cancer promoted tumor cell proliferation, migration, invasion and angiogenesis. 2182 29