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279736 occurrences (No.90 in the rank) during 5 years in the PubMed. [no cache] 500 found

245) The study revealed that CAF-specific TGFBR2 expression correlated with improved recurrence-free survival.

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PMID:24336330 DOI:10.1038/onc.2013.527

2015 Oncogene

* TGF-beta receptor type-2 expression in cancer-associated fibroblasts regulates breast cancer cell growth and survival and is a prognostic marker in pre-menopausal breast cancer.

- Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine with the capability to act as tumour suppressor or tumour promoter depending on the cellular context. TGF-beta receptor type-2 (TGFBR2) is the ligand-binding receptor for all members of the TGF-β family. Data from mouse model experiments demonstrated that loss of Tgfbr2 expression in mammary fibroblasts was linked to tumour initiation and metastasis. Using a randomised tamoxifen trial cohort including in total 564 invasive breast carcinomas, we examined TGFBR2 expression (n=252) and phosphorylation level of downstream target SMAD2 (pSMAD2) (n=319) in cancer-associated fibroblasts (CAFs) and assessed links to clinicopathological markers, prognostic and treatment-predictive values. The study revealed that CAF-specific TGFBR2 expression correlated with improved recurrence-free survival. Multivariate analysis confirmed CAF-TGFBR2 to be an independent prognostic marker (multivariate Cox regression, hazard ratio: 0.534, 95% (CI): 0.360-0.793, P=0.002). CAF-specific pSMAD2 levels, however, did not associate with survival outcome. Experimentally, TGF-β signalling in fibroblasts was modulated using a TGF-β ligand and inhibitor or through lentiviral short hairpin RNA-mediated TGFBR2-specific knockdown. To determine the role of fibroblastic TGF-β pathway on breast cancer cells, we used cell contact-dependent cell growth and clonogenicity assays, which showed that knockdown of TGFBR2 in CAFs resulted in increased cell growth, proliferation and clonogenic survival. Further, in a mouse model transfected CAFs were co-injected with MCF7 and tumour weight and proportion was monitored. We found that mouse xenograft tumours comprising TGFBR2 knockdown fibroblasts were slightly bigger and displayed increased tumour cell capacity. Overall, our data demonstrate that fibroblast-related biomarkers possess clinically relevant information and that fibroblasts confer effects on breast cancer cell growth and survival. Regulation of tumour-stromal cross-talk through fibroblastic TGF-β pathway may depend on fibroblast phenotype, emphasising the importance to characterise tumour microenvironment subtypes.

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(1)15 to	(19)4 types	(37)2 attention	(55)2 lineages
(2)9 sequence	(20)3 characteristics	(38)2 barriers	(56)2 measures
(3)7 and	(21)3 features	(39)2 computational	(57)2 miRNAs
(4)7 cell	(22)3 job	(40)2 constitutive	(58)2 molecular
(5)7 variations	(23)3 target	(41)2 criteria	(59)2 neuronal
(6)6 cognitive	(24)3 tendon	(42)2 deficits	(60)2 or
(7)6 genes	(25)3 therapy	(43)2 differences	(61)2 parameters
(8)6 surface	(26)3 type	(44)2 divergence	(62)2 phytotoxicity
(9)5 antibodies	(27)3 variation	(45)2 effect	(63)2 polymerase
(10)5 for	(28)2 null	(46)2 elements	(64)2 primers
(11)5 phobias	(29)2 ECM	(47)2 ethnocultural	(65)2 protein
(12)4 brain	(30)2 IgG	(48)2 extracellular	(66)2 proteins
(13)4 effects	(31)2 PCR	(49)2 fault	(67)2 recommendations
(14)4 growth	(32)2 age-dependent	(50)2 function	(68)2 requirements
(15)4 incidence	(33)2 analysis	(51)2 genetic	(69)2 self-efficacy
(16)4 manner	(34)2 antigen	(52)2 genomic	(70)2 targeted
(17)4 motor	(35)2 antigens	(53)2 information	(71)2 tests
(18)4 needs	(36)2 approach	(54)2 inhibitors

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--- WordNet output for specific --- =>特有の, 特効薬, 明確な, 特定の, 種の, はっきりした Overview of noun specific The noun specific has 2 senses (no senses from tagged texts) 1. particular, specific -- (a fact about some part (as opposed to general); "he always reasons from the particular to the general") 2. specific -- (a medicine that has a mitigating effect on a specific disease; "quinine is a specific for malaria") Overview of adj specific The adj specific has 4 senses (first 2 from tagged texts) 1. (39) specific -- ((sometimes followed by `to') applying to or characterized by or distinguishing something particular or special or unique; "rules with specific application"; "demands specific to the job"; "a specific and detailed account of the accident") 2. (5) specific -- (stated explicitly or in detail; "needed a specific amount") 3. specific -- (relating to or distinguishing or constituting a taxonomic species; "specific characters") 4. specific -- (being or affecting a disease produced by a particular microorganism or condition; used also of stains or dyes used in making microscope slides; "quinine is highly specific for malaria"; "a specific remedy"; "a specific stain is one having a specific affinity for particular structural elements") --- WordNet end ---