Abstract：
:Communication between cancer cells and the tumor microenvironment results in the modulation of complex signaling networks that facilitate tumor progression. Here, we describe a new mechanism of intercellular communication originating from large oncosomes (LO), which are cancer cell-derived, atypically large (1-10 μm) extracellular vesicles (EV). We demonstrate that, in the context of prostate cancer, LO harbor sustained AKT1 kinase activity, nominating them as active signaling platforms. Active AKT1 was detected in circulating EV from the plasma of metastatic prostate cancer patients and was LO specific. LO internalization induced reprogramming of human normal prostate fibroblasts as reflected by high levels of α-SMA, IL6, and MMP9. In turn, LO-reprogrammed normal prostate fibroblasts stimulated endothelial tube formation in vitro and promoted tumor growth in mice. Activation of stromal MYC was critical for this reprogramming and for the sustained cellular responses elicited by LO, both in vitro and in vivo in an AKT1-dependent manner. Inhibition of LO internalization prevented activation of MYC and impaired the tumor-supporting properties of fibroblasts. Overall, our data show that prostate cancer-derived LO powerfully promote establishment of a tumor-supportive environment by inducing a novel reprogramming of the stroma. This mechanism offers potential alternative options for patient treatment. Cancer Res; 77(9); 2306-17. ©2017 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Minciacchi VR,Spinelli C,Reis-Sobreiro M,Cavallini L,You S,Zandian M,Li X,Mishra R,Chiarugi P,Adam RM,Posadas EM,Viglietto G,Freeman MR,Cocucci E,Bhowmick NA,Di Vizio Ddoi
10.1158/0008-5472.CAN-16-2942subject
Has Abstractpub_date
2017-05-01 00:00:00pages
2306-2317issue
9eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-16-2942journal_volume
77pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Although in vivo targeting of tumors using fluorescently labeled probes has greatly gained in importance over the last few years, most of the clinically applied reagents lack tumor cell specificity. Our novel tumor cell-penetrating peptide-based probe (TPP) recognizes an epitope of Hsp70 that is exclusively present on...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-0413
更新日期：2014-12-01 00:00:00
abstract：:A monoclonal immunoglobulin M (IgM) antibody (38-13) which recognizes Burkitt's lymphoma (BL) cells, by reacting with the neutral glycolipid Gal alpha 1 leads to 4-Gal beta 1 leads to 4-Glc beta 1 leads to 1-ceramide, was recently characterized. This monoclonal IgM was coupled to either ricin A chain or gelonin. The t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:Recently the putative tumor suppressor gene p16INK4 was mapped to human chromosome 9p21, which is homologous to rat chromosome 5. Monosomy of rat chromosome 5 occurs with high frequency in rat kidney tumor-derived cell lines (ERC lines). Thus, we studied these lines in order to investigate the involvement of p15INK4B ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-04-15 00:00:00
abstract：:2-Phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) is classified as a relatively nontoxic selenium compound, probably because of its bound selenium moiety. In thiol-rich tissues, such as the kidneys, ebselen is converted into selenol intermediates. Selenols are nucleophilic agents which might be able to react with plat...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:The response to Photofrin II-induced photosensitization on the activities of mitochondrial monoamine oxidase (MAO) and adenylate kinase (AK) were studied in order to gain further insight into site specific effects. Utilizing intact mitochondria in vitro, both MAO, located on the cytoplasmic side of the outer mitochond...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-08-15 00:00:00
abstract：:We have produced a panel of monoclonal antibodies directed against a dimethylbenzanthracene-induced murine mammary tumor. Five rat-mouse hybridomas produced antibodies that bound to some murine mammary tumors, but not to normal renal adherent cells, lymphocytes, 3T3 fibroblasts, red blood cells, or mammary gland. One ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-08-01 00:00:00
abstract：:T cells expressing human leukemia virus (HTLV) type 1, the etiological agent of adult T-cell leukemia, are remarkably resistant to conventional chemotherapy, and the need for drugs that effectively kill these cells is apparent. Here we show that roscovitine, an inhibitor of cyclin-dependent kinases (CDKs), induces the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-12-01 00:00:00
abstract：:Pim serine/threonine kinases contribute to prostate tumorigenesis and therapeutic resistance, yet Pim kinase inhibitors seem to have only limited effects on prostate cancer cell survival. Because overexpression of Bcl-2 family members are implicated in chemotherapeutic resistance in prostate cancer, we investigated th...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-3240
更新日期：2012-01-01 00:00:00
abstract：:CI-921, an analogue of amsacrine with superior activity against in vivo and in vitro experimental tumor models, has been studied in 16 patients with solid tumors refractory to chemotherapy or for which conventional therapy does not exist. Thirty-nine cycles were given and doses escalated from 39 to 810 mg/m2. This tot...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-11-15 00:00:00
abstract：:The effects of estrogens on the growth and enzyme activities for androgen synthesis in a mouse Leydig cell tumor line (T 124958-R) were studied. The s.c. implantation of a diethylstilbestrol pellet resulted in a marked enhancement of the tumor growth. 5 alpha-Reductase activity (nmol/g/h) in tumors rapidly grown in th...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-02-01 00:00:00
abstract：:Phenobarbital (PB), a classical rodent hepatopromoter, remarkably enhances hepatocarcinogenesis initiated by diethylnitrosamine (DEN) in adult B6C3F1 mice. However, it is also known to strongly inhibit liver tumor development in the B6C3F1 mice initiated with DEN in their infancy. The present study aimed to elucidate ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-04-15 00:00:00
abstract：:Bloom syndrome is an autosomal recessive disorder whose characteristics include an increased risk for many types of cancers. In contrast to the homozygous mutations of Bloom syndrome, heterozygous carriers of BLM mutations may be at increased risk for developing colorectal cancer. We have screened 2,333 Jewish individ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-04-15 00:00:00
abstract：:Elevation of the DNA-unwinding helicase RECQL4, which participates in various DNA repair pathways, has been suggested to contribute to the pathogenicity of various human cancers, including gastric cancer. In this study, we addressed the prognostic and chemotherapeutic significance of RECQL4 in human gastric cancer, wh...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-2361
更新日期：2016-05-15 00:00:00
abstract：:Tumor-associated mutants of the p53 tumor suppressor protein exert biological activities compatible with an oncogenic gain of function. To explore the underlying molecular mechanism, we performed microarray analysis, comparing p53-null cells to mutant p53-expressing cells. One of the genes up-regulated in the presence...
journal_title：Cancer research
pub_type： 杂志文章,收录出版
doi：10.1158/0008-5472.CAN-04-1145
更新日期：2004-11-15 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：:Gamma-aminobutyric acid (GABA) functions primarily as an inhibitory neurotransmitter in the mature central nervous system, and GABA/GABA receptors are also present in nonneural tissues, including cancer, but their precise function in nonneuronal or cancerous cells has thus far been poorly defined. Through the genome-w...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-2099
更新日期：2007-10-15 00:00:00
abstract：:Clinical efficacy of PD-1/PD-L1 targeting relies upon the reactivation of tumor-specific but functionally impaired PD-1+ T cells present before therapy. Thus, analyzing early-stage primary tumors may reveal the presence of T cells that are not yet functionally impaired. In this study, we report that activated (HLA-DR+...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-1387
更新日期：2017-02-15 00:00:00
abstract：:Lymphocytes isolated from the peripheral blood of patients with nonmalignant and malignant disorders were studied for fluidity of membrane lipids and lateral mobility of concanavalin A (Con A) receptors. The degree of fluidity of the surface membrane lipid core was monitored quantitatively by fluorescence polarization...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-05-01 00:00:00
abstract：:Small molecule inhibitors of DNA repair are emerging as potent and selective anticancer therapies, but the sheer magnitude of the protein networks involved in DNA repair processes poses obstacles to discovery of effective candidate drugs. To address this challenge, we used a subtractive combinatorial selection approac...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-2361
更新日期：2011-03-01 00:00:00
abstract：:Endocannabinoids have been implicated in cancer. Increasing endogenous 2-arachidonoylglycerol (2-AG) by blocking its metabolism inhibits invasion of androgen-independent prostate cancer (PC-3 and DU-145) cells. Noladin ether (a stable 2-AG analog) and exogenous CB1 receptor agonists possess similar effects. Conversely...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-3136
更新日期：2004-12-15 00:00:00
abstract：:We observed stronger cytotoxic effect of CHS 828 on poly(ADP-ribose) polymerase-1(PARP-1) knock-out cells as compared with the normal counterpart. The proliferation of PARP-1 -/- cells was inhibited by a drug concentration approximately 3-fold lower than that in the normal cells. The monitoring of p53 levels revealed ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-08-01 00:00:00
abstract：:Bleomycin inhibits cellular RNA synthesis and the inhibition is nonspecific. The ratio of polyadenylate- [poly(A)] containing RNA to non-poly(A)-containing RNA in the drug-treated human lymphocytic cells, line Wil2, was the same as that in untreated cells. Poly(A) RNA isolated from untreated cells was used as a templa...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-05-01 00:00:00
abstract：:Four new human non-small cell lung cancer cell lines have been established in vitro. These cell lines have been characterized by (a) growth of a tumor in nude mice with histopathology similar to that of the primary, (b) isoenzyme patterns phenotypically human and distinct from each other, (c) distinguishing karyotypic...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：:Up-regulation of vascular endothelial growth factor (VEGF) expression is a major event leading to neovascularization in malignant gliomas. Hypoxia is believed to be the crucial environmental stimulus for this up-regulation. To critically assess this hypothesis, we asked whether the mechanisms defined previously for hy...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:The majority of colorectal cancers have lost/inactivated the p53 tumor suppressor gene. Using isogenic human colon cancer cells that differ only in their p53 status, we demonstrate that loss of p53 renders tumor cells relatively resistant to the topoisomerase I inhibitor, irinotecan. Whereas irinotecan-induced up-regu...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-2488
更新日期：2004-12-15 00:00:00
abstract：:Dicer1 functions as a tumor suppressor in mouse models. In humans, somatic mutations are associated with many cancers in adults, and patients with DICER1 syndrome with DICER1 germline mutations are susceptible to childhood cancers. Dicer is phosphorylated by the ERK-MAP kinase pathway and because this pathway is activ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-18-2460
更新日期：2019-05-15 00:00:00
abstract：:The effects of transforming growth factor-beta (TGF beta) on a human colon carcinoma cell line (MOSER) were investigated. TGF beta, at low concentrations (between 0.1 and 1.0 ng/ml), inhibited the proliferation of MOSER cells both in monolayer culture and soft agarose, in a dose-dependent manner. MOSER cells adapted t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-06-01 00:00:00
abstract：:We describe a method to postlabel, in vivo, biotinylated monoclonal antibodies pretargeted onto tumor deposits when most of the non-tumor-bound antibodies have already been cleared as avidin-bound complexes. The application of this principle to tumor detection by immunoscintigraphy was tested in 20 patients with histo...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:Cellular interaction with the extracellular milieu plays a significant role in normal biological and pathologic processes. Excessive degradation of basement membrane matrix by proteolytic enzymes is a hallmark of tumor invasion and metastasis, and aspartyl proteinase cathepsin D is implicated as a major contributor to...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-4767
更新日期：2007-04-15 00:00:00
abstract：:Cytogenetic analyses of intraspecies human HeLa X fibroblast hybrid cell populations have provided tentative evidence for the correlation of loss of a single copy of chromosomes 11 and 14 with reexpression of tumorigenicity. In this study paired combinations of nontumorigenic and tumorigenic segregant HeLa X fibroblas...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-12-01 00:00:00
