Abstract:
:The semaphorins and their receptors, the neuropilins and the plexins, are constituents of a complex regulatory system that controls axonal guidance. Moreover, many types of tumor cells express various members of semaphorins and receptors, but the biological activities within tumor mass and the signal transduction mechanism(s) they use are largely unknown. Here, we show that in asbestos-related malignant pleural mesothelioma (MPM), Semaphorin-6D (Sema6D) and its receptor plexin-A1 are frequently expressed and trigger a prosurvival program that promotes anchorage-independent growth of MPM cells. Interestingly, the same response is also controlled by the tyrosine kinase receptors of vascular endothelial growth factor (VEGF) through a nuclear factor-kappaB (NF-kappaB)-dependent pathway. We found that in MPM cells, plexin-A1 and VEGF-receptor 2 (VEGF-R2) are associated in a complex. Moreover, the presence of Sema6D promotes the tyrosine phosphorylation of VEGF-R2 in a plexin-A1-dependent manner. This is necessary for basal and Sema6D-induced NF-kappaB transcriptional activity, and NF-kappaB mediates tumor cell survival. Expression of Sema6D and plexin-A1 is induced by asbestos fibers and overexpression of plexin-A1 in nonmalignant mesothelial cells inhibits cell death after asbestos exposure. This work identifies a new biological function of semaphorins in cancer cells and suggests the involvement of an undescribed survival pathway during MPM tumorigenesis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Catalano A,Lazzarini R,Di Nuzzo S,Orciari S,Procopio Adoi
10.1158/0008-5472.CAN-08-3659subject
Has Abstractpub_date
2009-02-15 00:00:00pages
1485-93issue
4eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-08-3659journal_volume
69pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Although a Chinese hamster V79 cell-based assay for inhibitors of metabolic cooperation is currently available, the development of a human cell-based assay is desirable in order to avoid inappropriate extrapolation from animal cells to human cells. Cells derived from a human teratocarcinoma cell line (designated PA-1)...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Our previous studies demonstrated that reexpression of the alpha2beta1 integrin by a poorly differentiated breast carcinoma cell line, Mm5MT, resulted in dramatic reversion of a malignant phenotype to a differentiated epithelial phenotype. We hypothesized that reexpression of the alpha2beta1 integrin may regulate expr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-05-15 00:00:00
abstract::The binding of the papillomavirus E6 protein to E6AP and the induction of p53 degradation are common features of high-risk genital human papillomaviruses (HPV); cutaneous HPVs, on the other hand, lack these capacities. Nevertheless, several cutaneous HPV types of the beta-genus, such as HPV38 are associated with tumor...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-1307
更新日期:2010-09-01 00:00:00
abstract::B-cell precursor acute lymphoblastic leukemia (BCP-ALL/B-precursor ALL) is characterized by a high rate of tissue infiltration. The mechanism of BCP-ALL cell extravasation is not fully understood. In the present study, we have investigated the major carrier of carbohydrate selectin ligands in the BCP-ALL cell line NAL...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1459
更新日期:2008-02-01 00:00:00
abstract::In order to characterize the promoting activity of the peroxisome proliferator [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (WY-14,463), male F344 rats which received a single 150-mg/kg dose of diethylnitrosamine (DEN) were fed 0.1% WY-14,643 or 0.05% phenobarbital in the diet for 11, 22, or 54 wk. WY-14,6...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-06-15 00:00:00
abstract::The possibility of decreasing the gastrointestinal (GI) toxic effects of 5-fluorouracil (5-FU) on the digestive tract such as its injury of cells and induction of diarrhea, without reducing its antitumor activity, was investigated in rats. Oxonic acid was found to inhibit the phosphorylation of 5-FU to 5-fluorouridine...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::Quantitative micromethods have been used for measuring reactive protein thiols (PSHr), total reactive protein sulfur (TRPS), total protein thiols (PSHt), and protein disulfides (PDS) in fixed frozen sections of human uterine cervix. PSHr and TRPS were stained using 2,2'-dihydroxy-6,6'-dinaphthyl disulfide; PSHt and PD...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-10-15 00:00:00
abstract::Chemical and biological studies are presented for a new series of platinum(II) antitumor agents that violate the classical structure-activity relationships established for platinum complexes. These new agents, which have demonstrated activity against murine and human tumor systems, are cis-[Pt(NH3)2(Am)Cl]+ cations, i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
abstract::The possible contribution of endocrine disrupters to human disease, particularly those compounds that modulate the estrogen receptor (ER), has recently drawn considerable attention. The tissue specificity of effects mediated by the ER is well recognized, although the mechanism of this specificity is not understood suf...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::Monoclonal antibody (MAb) B72.3 was generated using a membrane-enriched fraction of a human mammary carcinoma biopsy. It has demonstrated reactivity to the majority of human adenocarcinomas including colorectal, gastric, pancreatic, ovarian, endometrial, mammary, and non-small cell lung cancer and no or weak reactivit...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-08-15 00:00:00
abstract::We compared the effect of nine N-nitroso compounds, given by gavage to adult rats, on specific radioactivity of the trichloroacetic acid-precipitable liver proteins, 1 hr after the injection of [14C]leucine. The specific radioactivity was decreased by dimethylnitrosamine, diethylnitrosamine, methyl-n-butylnitrosamine,...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract::The Adenomatous polyposis coli (Apc) gene is mutated in up to 80% of sporadic colorectal cancers. After Apc loss, there is deregulation of the Wnt signaling pathway and transactivation of T-cell factor/leukemia enhancing factor target genes such as C-Myc. This review focuses on recent data highlighting the importance ...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-07-5558
更新日期:2008-07-01 00:00:00
abstract::Genomic DNA from 14 basal cell carcinoma biopsies was screened for the presence of mutations in the p53 gene, using the polymerase chain reaction followed by direct DNA sequencing. Heterozygous mutations were detected in 7 of 14 (50%) samples investigated. All mutations were G:C-A:T transitions, and five (71%) of thes...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::The MCT-1 oncogene was originally identified from lymphoma cell lines. Herein we establish that MCT-1 is highly expressed in 85% of human diffuse large B-cell lymphomas (DLBCL) and that knocking down MCT-1 by a specific short hairpin RNA in DLBCL cells induces apoptosis, supporting a critical role for MCT-1 in DLBCL c...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-1606
更新日期:2009-10-01 00:00:00
abstract::Recent in vitro studies of the epidermal growth factor receptor (EGFR) family have revealed complex signaling interactions involving the production of ligand-mediated heterodimers synergistic for the transformation of cells in vitro. In a series of 70 patients with childhood medulloblastoma, we have used immunohistoch...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::There is widespread agreement that cancer gene discovery requires high-quality tumor samples. However, whether primary tumors or cultured samples are superior for cancer genomics has been a longstanding subject of debate. This debate has recently become more important because federally funded cancer genomics has been ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-1055
更新日期:2009-07-15 00:00:00
abstract::We have examined the effects of protein kinase C (PK-C) stimulation and cytosolic Ca2+ elevation on the in vitro induction of non-histocompatibility-restricted tumoricidal activity from human peripheral blood lymphocytes. The tumor cytolytic activity, as well as the number of cells recovered from interleukin 2 (IL-2)-...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract::The mechanism by which gonadotropin-releasing hormone (GnRH) agonists and antagonists inhibit tumor cell growth and proliferation is controversial. Direct mediation of the antitumor effects through the high-affinity GnRH receptors has been questioned because of the low level of expression of receptors on the tumor cel...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-10-15 00:00:00
abstract::The anticarcinogenic activities of retinoic acid (RA) are believed to be mediated by the nuclear RA receptor (RAR) and by the RA-binding protein cellular RA-binding protein-II (CRABP-II). In MCF-7 mammary carcinoma cells, growth inhibition by RA entails an early cell cycle arrest followed by induction of apoptosis. He...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-0989
更新日期:2007-01-15 00:00:00
abstract::IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surv...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-17-0428
更新日期:2017-06-01 00:00:00
abstract::N-Demethylated metabolites of the antineoplastic agent hexamethylmelamine were synthesized, and their toxicities and antitumor activities were determined in vivo. Determinations of the lethal dose for 10% of the male C57BL X DBA/2 F1 (hereafter called BD2F1) mice showed hexamethylmelamine toxicity to be decreased by N...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-10-01 00:00:00
abstract::High expression of VEGFC predicts adverse prognosis in acute myeloid leukemia (AML). We therefore explored VEGFC-targeting efficacy as an AML therapy using a VEGFC mAb. VEGFC antibody therapy enforced myelocytic differentiation of clonal CD34+ AML blasts. Treatment of CD34+ AML blasts with the antibody reduced expansi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-0250
更新日期:2018-10-15 00:00:00
abstract::Regional measurements of blood flow (F) were performed in transplanted intracerebral RG-2 rat gliomas using [14C]iodoantipyrine, Kety-Schmidt blood flow equations, and quantitative autoradiography. Twenty-nine intracranial tumors in ten rats were analyzed by location; 18 intraparenchymal, seven meningeal, two third-ve...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-07-01 00:00:00
abstract::Genetic instability plays a central role in the development and progression of human cancer. Two major classes of genetic instability, microsatellite instability (MSI) and chromosome instability (microsatellite stable; MSS), are best understood in the context of colon cancer, where MSI tumors represent approximately 1...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-4163
更新日期:2005-10-15 00:00:00
abstract::Two human ovarian tumor cell lines (SK-OV-3 and TR175), established from patients previously treated with alkylating agents, but not with cisplatin, expressed greater than 23-fold differences in cisplatin sensitivities in vitro. Cisplatin resistance in SK-OV-3 cells appeared to be associated with increased levels of g...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::EJ-ras oncogene-induced malignant transformation is characterized by a series of changes in cell surface carbohydrates and cell-cell and cell-matrix interactions. Here, we show that EJ-ras-transformed NIH-3T3 fibroblasts acquired a migratory phenotype on laminin-1 surfaces. Such a phenotype was accompanied by overexpr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::We review and compare statistical methods for the analysis of in vivo tumor growth experiments. The methods most commonly used are deficient in that they have either low power or misleading type I error rates. We propose a set of multivariate statistical modeling methods that correct these problems, illustrating their...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-12-15 00:00:00
abstract::Astrocytoma, the most common brain tumor in humans, is usually malignant and virtually incurable. Two types of malignant astrocytomas can be distinguished histopathologically: anaplastic astrocytoma and glioblastoma multiforme. Studies using DNA markers that detect restriction fragment length polymorphisms have shown ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-09-15 00:00:00
abstract::Fibroblast growth factor (FGF) receptor (FGFR) substrate 2 (FRS2) is an adaptor protein that plays a critical role in FGFR signaling. FRS2 is located on chromosome 12q13-15 that is frequently amplified in liposarcomas. The significance of FRS2 and FGFR signaling in high-grade liposarcomas is unknown. Herein, we first ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-2086
更新日期:2013-02-15 00:00:00
abstract::Insulin-like growth factors (IGFs) have mitogenic and antiapoptotic properties and have been implicated in the development of lung cancer. The effects of IGFs are modulated by insulin-like growth factor binding proteins (IGFBPs). This study explored the effects of IGFBP-3 on non-small cell lung cancer (NSCLC) cells af...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-06-15 00:00:00