Abstract：
:Hepatocellular carcinoma (HCC) typically develops in cirrhosis, a condition characterized by Hedgehog (Hh) pathway activation and accumulation of Hh-responsive myofibroblasts. Although Hh signaling generally regulates stromal-epithelial interactions that support epithelial viability, the role of Hh-dependent myofibroblasts in hepatocarcinogenesis is unknown. Here, we used human HCC samples, a mouse HCC model, and hepatoma cell/myofibroblast cocultures to examine the hypothesis that Hh signaling modulates myofibroblasts' metabolism to generate fuels for neighboring malignant hepatocytes. The results identify a novel paracrine mechanism whereby malignant hepatocytes produce Hh ligands to stimulate glycolysis in neighboring myofibroblasts, resulting in release of myofibroblast-derived lactate that the malignant hepatocytes use as an energy source. This discovery reveals new diagnostic and therapeutic targets that might be exploited to improve the outcomes of cirrhotic patients with HCCs.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Chan IS,Guy CD,Chen Y,Lu J,Swiderska-Syn M,Michelotti GA,Karaca G,Xie G,Krüger L,Syn WK,Anderson BR,Pereira TA,Choi SS,Baldwin AS,Diehl AMdoi
10.1158/0008-5472.CAN-12-1068subject
Has Abstractpub_date
2012-12-15 00:00:00pages
6344-50issue
24eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-1068journal_volume
72pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Prostate-specific membrane antigen (PSMA) is expressed in normal human prostate epithelium and is highly up-regulated in prostate cancer. We previously reported a series of novel small molecule inhibitors targeting PSMA. Two compounds, MIP-1072, (S)-2-(3-((S)-1-carboxy-5-(4-iodobenzylamino)pentyl)ureido)pentanedioic a...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-1682
更新日期：2009-09-01 00:00:00
abstract：:Normal human cells can be transformed to anchorage-independent growth by transfection with DNA from MOLT-4 lymphoblasts, derived from a patient with acute lymphocytic leukemia. Cells were treated with polyethylene glycol 6000, and DNA was administered as a calcium phosphate coprecipitate . The transforming activity of...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-07-01 00:00:00
abstract：:The proliferation rate of HT29 colon carcinoma cells was decreased by the multitargeted antifolate (MTA), LY231514. This effect correlated with a buildup of cells near the G1-S interface after 24 h of incubation, and a synchronized progression of the population through S phase during the next 24 h. MTA treatment (0.03...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-08-01 00:00:00
abstract：:Angiogenesis inhibitor TNP-470, 6-O-(N-chloroacetyl-carbamoyl)-fumagillol, semisynthetic analogue of fumagillin, has strong inhibitory activities against in vivo tumor growth and metastasis in a wide variety of tumors. However, it is still unknown whether this agent inhibits bone metastasis. We examined the effects of...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
abstract：:The effects of tumor-promoting phorbol diesters on ornithine decarboxyalse (ODC) activity and DNA synthesis in normal and chemically transformed hamster embryo fibroblasts (HEF) in culture were studied. Only those phorbol diesters with promoting activity in mouse skin induced ODC in HEF. ODC was induced in both cell t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-11-01 00:00:00
abstract：:The mechanism of action of the clinically used iron(III) chelator, desferrioxamine (DFO), on preventing iron (Fe) uptake from transferrin (Tf) has been investigated using the human melanoma cell line SK-MEL-28. This investigation was initiated due to the paucity of information on the mechanisms of action of DFO in neo...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
abstract：:Increasing the expression of c-FMS (colony-stimulating factor 1 receptor) by introduction of a transgene reduced the concentration of retinoic acid or 1,25-dihydroxy vitamin D3 needed to cause myeloid or monocytic cell differentiation and hypophosphorylation of the retinoblastoma tumor suppressor protein (RB) typicall...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-05-15 00:00:00
abstract：:The calcium channel blocker verapamil has been shown to reverse multidrug resistance (T. Tsuruo et al., Cancer Res. 41: 1967-1972, 1981), but the mechanism of action of this agent has not been fully elucidated. A radioactive photoactive analogue of verapamil, N-[benzoyl-3,5-3H-(+/-)-5-[(3,4-dimethoxyphenetyl)methylami...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-09-15 00:00:00
abstract：:Anaplastic large cell lymphomas (ALCL) are mainly characterized by the reciprocal translocation t(2;5)(p23;q35) that involves the anaplastic lymphoma kinase (ALK) gene and generates the fusion protein NPM-ALK with intrinsic tyrosine kinase activity. NPM-ALK triggers several signaling cascades, leading to increased cel...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-4350
更新日期：2007-05-01 00:00:00
abstract：:Transforming growth factor beta-1 (TGF-beta1) is a potent inhibitor of hepatocyte growth both in vivo and in vitro. In this study, we analyzed the effects of TGF-beta1 on both naturally occurring and diethylnitrosamine-induced hepatocarcinogenesis using single transgenic TGF-beta1 and double transgenic c-myc/TGF-beta1...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-06-01 00:00:00
abstract：:Osteosarcoma is the most common malignant bone tumor in children. Osteosarcoma patients who respond poorly to chemotherapy are at a higher risk of relapse and adverse outcome. Therefore, it was the aim of this study to identify prognostic factors at the time of diagnosis to characterize the genes predictive of poor su...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-2463
更新日期：2005-03-01 00:00:00
abstract：:The D98/AH-2 cell line (a subline of HeLa) expresses a form of alkaline phosphatase (ALP) which closely resembles the adult and fetal intestinal forms of ALP. To characterize this ectopic form of ALP, four monoclonal antibodies were raised against D98/AH-2 ALP, and their binding with ALPs from D98/AH-2 cells, placenta...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-02-01 00:00:00
abstract：:In a preceding paper for brain tumors, we demonstrate a tight association between regional hypermethylation at locus D17S5 of chromosome 17p and allelic loss of this chromosome. Because 17p allelic losses occur at the earliest stages of brain tumors, the exact temporal relationship between this event and the hypermeth...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-06-15 00:00:00
abstract：:A previous study demonstrated inhibition of growth of primary rat mammary carcinomas after infusion of tumor-bearer plasma absorbed against Sepharose derivatives. In this report we have quantitated changes in individual complement components that occur during absorption of rat plasma with Sepharose derivatives and def...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-09-01 00:00:00
abstract：:Rat mammary carcinomas were induced by directly inserting activated neu or ras genes into in situ rat mammary ductal cells using replication-defective retroviral vectors. neu was over 200 times more potent than ras in inducing rat mammary carcinomas. Ovariectomy 2 days postinfection dramatically reduced the occurrence...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-08-01 00:00:00
abstract：:Metastasis requires cytoskeletal remodeling for migration, adhesion, and extravasation of metastatic cells. Although protein kinase C (PKC) is involved in tumor promotion/progression and cytoskeletal remodeling, its role in metastasis has not been defined. PKCdelta levels are increased in highly metastatic 13762NF mam...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-07-01 00:00:00
abstract：:Isoprenoid inhibitors are being evaluated as agents for the treatment of cancer. Their antitumor activity is attributed to inhibition of post-translational modification of Ras, which is crucial for its translocation and attachment to the plasma membrane, and ultimate involvement in signal transduction. However, whethe...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-3416
更新日期：2006-01-15 00:00:00
abstract：:To study the long-term effects of estrogen deprivation on breast cancer, MCF-7Ca human estrogen receptor-positive breast cancer cells stably transfected with human aromatase gene were cultured in the steroid-depleted medium for 6 to 8 months until they had acquired the ability to grow. Proliferation of these cells (UM...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-4092
更新日期：2005-05-01 00:00:00
abstract：:Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths in the United States. The deoxynucleoside analogue gemcitabine is among the most effective therapies to treat PDAC, however, nearly all patients treated with gemcitabine either fail to respond or rapidly develop resistance. One hallmark of PDA...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-19-0960
更新日期：2019-11-15 00:00:00
abstract：:Normal or immortal epithelial cells are sensitive to a form of apoptosis, commonly referred to as anoikis, which is induced by detachment from the extracellular matrix (ECM). In contrast, development of carcinomas is associated with acquisition of cellular resistance to anoikis. However, whether human cancer cells dep...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-06-15 00:00:00
abstract：:The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual specificity protein phosphatase that dephosphorylates Cdk2 on threonine 160 in a cyclin-dependent manner. To investigate whether mutations of this enzyme occur in hepatocellular carcinoma (HCC), KAP mRNA was analyzed by reverse tran...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-09-01 00:00:00
abstract：:Most solid malignancies display interstitial hypertension and a poor uptake of anticancer drugs. Platelet-derived growth factor (PDGF) and the cognate tyrosine kinase receptors are expressed in many tumors. Signaling through PDGFbeta receptors was shown recently to increase interstitial fluid pressure (IFP) in dermis ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：:Estrogen receptor (ER)-positive human breast cancer cells are hormonally regulated and are inhibited by retinoids, whereas most ER-negative breast cancer cells are not. Here, we compared retinoid-induced transcriptional activation and growth inhibition in the ER-negative breast cancer cell line MDA-MB-231, stably tran...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-11-15 00:00:00
abstract：:We demonstrate here that paclitaxel exposure to RPMI-1788 B lymphoblasts caused a dose- and time-dependent increase in nuclear factor activator protein 1 (AP-1) DNA binding activity. The basal DNA binding activities of nuclear factors NF-kappaB and Ets were not affected by paclitaxel. Consistent with these biochemical...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-01-15 00:00:00
abstract：:By molecular genetic approach using polymorphic DNA markers which detect allelic deletion at specific chromosomal loci, we analyzed 30 human stomach cancers for possible loss of chromosomal heterozygosity. We analyzed 25 loci on 18 different chromosomes covering regions frequently deleted in several types of cancers. ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：:The nucleus has been shown to be a site for the inositol lipid cycle that can be affected by treatment of quiescent cells with growth factors such as insulin-like growth factor I (IGF-I). Indeed, the exposure of Swiss 3T3 cells to IGF-I results in a rapid and transient increase in nuclear phospholipase C (PLC) beta1 a...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-06-01 00:00:00
abstract：:The combinations of amphotericin B (AmB) with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) or 2-cyclohexyl isocyanate, the carbamoylating decomposition product of CCNU, were more potent in lysing HL-60 cells than the combinations of AmB with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) or 2-chloroethyl isocyana...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
abstract：:As previously reported for natural killer (NK) cells of normal individuals, prior incubation of peripheral blood lymphocytes from cancer patients with human normal serum or monomeric immunoglobulin G reduced their subsequent capacity to kill K562 target cells in a 4-h 51Cr release assay. The NK activity of such treate...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
abstract：:Multiple myeloma is a B-cell malignancy characterized by the uncontrolled growth of plasma cells in the bone marrow and the development of osteolytic bone disease. Myeloma cells express the receptor activator of nuclear factor kappaB ligand (RANKL), induce RANKL expression in the bone marrow, and down-regulate express...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-1287
更新日期：2007-01-01 00:00:00
abstract：:An animal lectin purified from loach (Misgurnus anguillicaudatus) eggs induced release of cytotoxin from fresh bone marrow cells from mice, although the other lectins tested, wheat germ agglutinin, concanavalin A, and phytohemagglutinin did not. The cytotoxin released from bone marrow cells was a heat-labile protein w...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
