TGF-β1 Is Present at High Levels in Wound Fluid from Breast Cancer Patients Immediately Post-Surgery, and Is Not Increased by Intraoperative Radiation Therapy (IORT)

Abstract

In patients with low-risk breast cancer, intraoperative radiotherapy (IORT) during breast-conserving surgery is a novel and convenient treatment option for delivering a single high dose of irradiation directly to the tumour bed. However, edema and fibrosis can develop after surgery and radiotherapy, which can subsequently impair quality of life. TGF- β is a strong inducer of the extracellular matrix component hyaluronan (HA). TGF-β expression and HA metabolism can be modulated by irradiation experimentally, and are involved in edema and fibrosis. We therefore hypothesized that IORT may regulate these factors.Wound fluid (WF) draining from breast lumpectomy sites was collected and levels of TGF-β1 and HA were determined by ELISA. Proliferation and marker expression was analyzed in primary lymphatic endothelial cells (LECs) treated with recombinant TGF-β or WF. Our results show that IORT does not change TGF-β1 or HA levels in wound fluid draining from breast lumpectomy sites, and does not lead to accumulation of sHA oligosaccharides. Nevertheless, concentrations of TGF-β1 were high in WF from patients regardless of IORT, at concentrations well above those associated with fibrosis and the suppression of LEC identity. Consistently, we found that TGF-β in WF is active and inhibits LEC proliferation. Furthermore, all three TGF-β isoforms inhibited LEC proliferation and suppressed LEC marker expression at pathophysiologically relevant concentrations.Given that TGF-β contributes to edema and plays a role in the regulation of LEC identity, we suggest that inhibition of TGF-β directly after surgery might prevent the development of side effects such as edema and fibrosis.

Diagnostic Significance of Beclin-1 and Transforming Growth Factor β in Breast Cancer

“…Our finding is supported by El-Aziz et al, [17] who revealed that the level of TGF-β was considerably higher in malignant groups than normal control group with p value (<0.0001). The results of the present study was supported by Scherer et al, [18] who detected the level of TGF-β in breast cancer patients; he found that its level was increased. In the current study, ROC curve of beclin-1 showed 95% sensitivity and 98.5% specificity and this is supported by Harb, et al, [19] who reported that the sensitivity of beclin-1 as a predictor for advanced stage of IDC was 85.5% and the specificity was 98.5%.…”

Does Direct and Indirect Exposure to Ionising Radiation Influence the Metastatic Potential of Breast Cancer Cells

“…Boothe et al reported that TGF-β1 serum levels of breast cancer patients can be used as an early biomarker for radiation-induced fibrosis post RT [44]. Evidence was also found for a high level of TGF-β1 in the breast cancer patients' wound fluids 24 h following surgery [45].…”

Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer

“…High plasma or serum levels of TGF-β1 before RT have been associated with fibrosis of the breast [ 4 , 5 ]. Regardless of whether patients received intra-operative RT or not, TGF-β1 concentrations in wound fluid were similar 24 h after surgery [ 7 ]. The relationship between TGF-β1 and RT has been most extensively studied in lung cancer patients.…”