Abstract 3062
Background
Anthracycline/taxane-based chemotherapy is frequently used to treat breast cancer. However, not all patients respond to chemotherapy due to naturalor acquired chemo-resistance. Glutathione S-transferase P1(GSTP1), which belongs to the family of phase II metabolic enzymes, has been reported to function in detoxifying several anti-cancer drugs by conjugating them with glutathione.
Methods
We identified GSTP1 as a drug-resistance-related factor by microarray. Then, we used cell apoptosis and immunofluorescence staining to confirm the ability of GSTP1-containing exosomes in conferring drug resistance. And the knockdown of GSTP1 gene was performed to found the influence of drug-resistance. Furthermore, the role of GSTP1 and its relationship with exosomes was proved by analysed 40 pairs of breast cancer tissues by IHC. Then, the levels of GSTP1 in serum exosomes were detected in 28 patients treated with neoadjuvant chemotherapy(NAC).
Results
By microarray data, we found that GSTP1, which located in extracellular exosome, is higher in Adriamycin(ADR)-resistant cell line compared with its parental cell line. Then, we also confirmed a higher expression of GSTP1 protein in ADR-resistant cells by immunofluorescence staining and western blot. Moreover, the addition of GSTP1-containing exosomes can increase the resistance to ADR in sensitive cells. Also, we found that a higher expression GSTP1 in the PD/SD group than in the PR/CR group in 40 paired samples collected before and after chemotherapy. Similar results were obtained for the exosomal marker tumor susceptibility gene 101 protein (TSG101), which also increased in the cytoplasm after chemotherapy. We further explored the levels of GSTP1 in serum exosomes of 28 patients treated with anthracycline/taxane-based NAC, and discovered that the levels of GSTP1 in exosomes from patients in the PD/SD group were higher than those in the PR/CR group.
Conclusions
GSTP1-containing exosomes appeared to be essential in conferring resistance to anti-cancer drugs. We explored the predictive role of GSTP1 in circulating exosomes as a biomarker for chemo-sensitivity in patients treated with anthracycline/taxane-based chemotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jinhai Tang.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5747 - The routine use of sentinel lymph node biopsy in high risk DCIS lesions is not justified
Presenter: Fanny Preat
Session: Poster Display session 2
Resources:
Abstract
1837 - Oncological impact of re-excision for positive margin status after breast conserving surgery in invasive breast cancer
Presenter: Kenjiro Jimbo
Session: Poster Display session 2
Resources:
Abstract
4347 - Pneumonitis and fibrosis after breast cancer radiation.
Presenter: Jarle Karlsen
Session: Poster Display session 2
Resources:
Abstract
2280 - Prognosis of mastectomy with reconstruction after neoadjuvant chemotherapy: a nationwide study in Korean Breast Cancer Society
Presenter: Sungmin Park
Session: Poster Display session 2
Resources:
Abstract
804 - A negative prognosis of radiotherapy-induced lower lymphocyte to monocyte ratio in patients with breast cancer
Presenter: Chang-ik Yoon
Session: Poster Display session 2
Resources:
Abstract
2701 - Patient data to monitor clinical patterns in early and advanced breast cancer in Europe
Presenter: Francesco Giusti
Session: Poster Display session 2
Resources:
Abstract
1437 - A critical appraisal of quality indicators of breast cancer treatment in Belgium
Presenter: Didier Verhoeven
Session: Poster Display session 2
Resources:
Abstract
1534 - Predictors of adherence among post-menopausal women receiving adjuvant endocrine therapy for breast cancer in Ontario, Canada
Presenter: Phillip Blanchette
Session: Poster Display session 2
Resources:
Abstract
4363 - Evaluation of endocrine therapy and patients preferences in early breast cancer: results of Elena study
Presenter: Emilia Montagna
Session: Poster Display session 2
Resources:
Abstract
2679 - Baseline Quality of life (QoL) and chemotherapy related toxicities (CRT) in localized breast cancer (BC) patients (pts): the French multicentric prospective CANTO cohort study
Presenter: Idlir Licaj
Session: Poster Display session 2
Resources:
Abstract