ArticleOncotarget2016
High expression of intratumoral stromal proteins is associated with chemotherapy resistance in breast cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics.International journal of cancer · 2020Trial
- Immunohistochemical Characterization of Tenascin-C Expression in Treatment-Naïve Breast Cancer: An Exploratory Pilot Study.Current issues in molecular biology · 2026Article
- FGFR‑related phenotypic and functional profile of CAFs in prognostication of breast cancer (Review).International journal of oncology · 2024Review
- Duocarmycin SA Reduces Proliferation and Increases Apoptosis in Acute Myeloid Leukemia Cells In Vitro.International journal of molecular sciences · 2024Article
- Plasma THBS1 as a predictive biomarker for poor prognosis and brain metastasis in patients with HER2-enriched breast cancer.International journal of clinical oncology · 2024Article
- Role of integrin β1 and tenascin C mediate TGF-SMAD2/3 signaling in chondrogenic differentiation of BMSCs induced by type I collagen hydrogel.Regenerative biomaterials · 2024Article
- SPARC: a potential target for functional nanomaterials and drugs.Frontiers in molecular biosciences · 2023Review
- Identification of prognostic cancer-associated fibroblast markers in luminal breast cancer using weighted gene co-expression network analysis.Frontiers in oncology · 2023Article
- Tissue Rigidity Increased during Carcinogenesis of NTCU-Induced Lung Squamous Cell Carcinoma In Vivo.Biomedicines · 2022Article
- Identification of tumor biomarkers for pathological complete response to neoadjuvant treatment in locally advanced breast cancer.Breast cancer research and treatment · 2022Article
- Towards targeting of shared mechanisms of cancer metastasis and therapy resistance.Nature reviews. Cancer · 2022Review
- Revisiting the Tenascins: Exploitable as Cancer Targets?Frontiers in oncology · 2022Review
- Upper aerodigestive tract carcinoma: Development of a (epi)genomic predictive model for recurrence and metastasis.Oncology letters · 2020Article
- Immunohistochemical analysis of the expression of cancer-associated fibroblast markers in esophageal cancer with and without neoadjuvant therapy.Virchows Archiv : an international journal of pathology · 2020Article
- Mechanisms behind prometastatic changes induced by neoadjuvant chemotherapy in the breast cancer microenvironment.Breast cancer (Dove Medical Press) · 2019Article
- Identification of key pathways and biomarkers in sorafenib-resistant hepatocellular carcinoma using bioinformatics analysis.Experimental and therapeutic medicine · 2018Article
- Significance of calreticulin as a prognostic factor in endometrial cancer.Oncology letters · 2018Article
- Esophageal adenocarcinoma microenvironment: Peritumoral adipose tissue effects associated with chemoresistance.Cancer science · 2017Article
- Identification of LRP-1 as an endocytosis and recycling receptor for β1-integrin in thyroid cancer cells.Oncotarget · 2017Article
- Curcumin combined with cis-platinum promote the apoptosis of human colorectal cancer HT29 cells and mechanism.International journal of clinical and experimental pathology · 2017Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We studied the changes of intratumoral stromal proteins including THBS1, TNC, FN, SPARC and α-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 α-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 TNC-associated 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 β1/mTOR pathway. Thus, up-regulation of THBS1, TNC, FN, SPARC and α-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 β1/mTOR pathway, suggesting that therapies targeting integrin β1/mTOR pathway may be a promising strategy to overcome chemotherapy resistance.
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