Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.10894
DC FieldValue
dc.titleHigh expression of intratumoral stromal proteins is associated with chemotherapy resistance in breast cancer
dc.contributor.authorWang, T
dc.contributor.authorSrivastava, S
dc.contributor.authorHartman, M
dc.contributor.authorBuhari, S.A
dc.contributor.authorChan, C.-W
dc.contributor.authorIau, P
dc.contributor.authorKhin, L.W
dc.contributor.authorWong, A
dc.contributor.authorTan, S.-H
dc.contributor.authorGoh, B.-C
dc.contributor.authorLee, S.-C
dc.date.accessioned2020-09-03T10:31:43Z
dc.date.available2020-09-03T10:31:43Z
dc.date.issued2016
dc.identifier.citationWang, T, Srivastava, S, Hartman, M, Buhari, S.A, Chan, C.-W, Iau, P, Khin, L.W, Wong, A, Tan, S.-H, Goh, B.-C, Lee, S.-C (2016). High expression of intratumoral stromal proteins is associated with chemotherapy resistance in breast cancer. Oncotarget 7 (34) : 55155-55168. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.10894
dc.identifier.issn19492553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174109
dc.description.abstractWe studied the changes of intratumoral stromal proteins including THBS1, TNC, FN, SPARC and a-SMA, following neoadjuvant chemotherapy. The underlying mechanisms by which THBS1 and TNC regulated resistance to docetaxel were further studied using functional studies. 100 patients with newly diagnosed breast cancer were treated with alternating sequential doxorubicin and docetaxel. Immunohistochemistry (IHC) staining for stromal proteins was performed on pre- and post-treatment core biopsies respectively. THBS1 and TNC were further validated with IHC in an independent cohort of 31 patients. A high baseline combined expression score of the 5 stromal proteins predicted independently for poor progression-free (HRadjusted 2.22, 95% CI 1.06-4.64) and overall survival (HRadjusted 5.94, 95% CI 2.25-15.71). After 1-2 cycles of chemotherapy, increased expression of THBS1, TNC, FN, SPARC and a-SMA was seen in patients with subsequent pathological lymph node involvement at surgery. Increased expression of THBS1 and TNC compared to baseline was also seen in intrinsically resistant tumors, but not in sensitive ones. Both THBS1 and TNCassociated chemoresistance were confirmed in an independent validation cohort. Exogenous THBS1 and TNC protected MCF-7 cells against proliferation inhibition induced by docetaxel through activating integrin ß1/mTOR pathway. Thus, upregulation of THBS1, TNC, FN, SPARC and a-SMA following neoadjuvant chemotherapy was associated with chemotherapy resistance in breast cancer patients. Functional studies showed THBS1 and TNC to mediate chemoresistance through the integrin ß1/mTOR pathway, suggesting that therapies targeting integrin ß1/mTOR pathway may be a promising strategy to overcome chemotherapy resistance.
dc.sourceUnpaywall 20200831
dc.subjectalpha smooth muscle actin
dc.subjectbeta1 integrin
dc.subjectdocetaxel
dc.subjectdoxorubicin
dc.subjectestrogen receptor
dc.subjectFN protein
dc.subjectmammalian target of rapamycin
dc.subjectoncoprotein
dc.subjectSPARC protein
dc.subjectTHBS1 protein
dc.subjectTNC protein
dc.subjectunclassified drug
dc.subjectbeta1 integrin
dc.subjectMTOR protein, human
dc.subjecttarget of rapamycin kinase
dc.subjecttenascin
dc.subjectthrombospondin 1
dc.subjectthrombospondin-1, human
dc.subjectArticle
dc.subjectbreast cancer
dc.subjectbreast surgery
dc.subjectcancer adjuvant therapy
dc.subjectcancer growth
dc.subjectcancer resistance
dc.subjectcancer survival
dc.subjectclinical feature
dc.subjectcohort analysis
dc.subjectcontrolled study
dc.subjectdrug efficacy
dc.subjectfemale
dc.subjecthuman
dc.subjecthuman tissue
dc.subjectimmunohistochemistry
dc.subjectmajor clinical study
dc.subjectMCF 7 cell line
dc.subjectmultiple cycle treatment
dc.subjectoutcome assessment
dc.subjectoverall survival
dc.subjectphase 2 clinical trial
dc.subjectprediction
dc.subjectprotein determination
dc.subjectprotein expression
dc.subjectprotein function
dc.subjectrandomized controlled trial
dc.subjecttumor biopsy
dc.subjectupregulation
dc.subjectadult
dc.subjectaged
dc.subjectbreast tumor
dc.subjectchemistry
dc.subjectdrug resistance
dc.subjectmiddle aged
dc.subjectmortality
dc.subjectpathology
dc.subjectphysiology
dc.subjectsignal transduction
dc.subjecttumor cell line
dc.subjectAdult
dc.subjectAged
dc.subjectBreast Neoplasms
dc.subjectCell Line, Tumor
dc.subjectDrug Resistance, Neoplasm
dc.subjectFemale
dc.subjectHumans
dc.subjectIntegrin beta1
dc.subjectMiddle Aged
dc.subjectSignal Transduction
dc.subjectTenascin
dc.subjectThrombospondin 1
dc.subjectTOR Serine-Threonine Kinases
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentDEPT OF SURGERY
dc.contributor.departmentDEAN'S OFFICE (MEDICINE)
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.description.doi10.18632/oncotarget.10894
dc.description.sourcetitleOncotarget
dc.description.volume7
dc.description.issue34
dc.description.page55155-55168
Appears in Collections:Elements
Staff Publications

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_18632_oncotarget_10894.pdf7.23 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

15
checked on Feb 24, 2021

Page view(s)

45
checked on Feb 26, 2021

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.