This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Belletti, B. Articles by Massarut, S. PubMed PubMed Citation Articles by Belletti, B. Articles by Massarut, S.

Targeted Intraoperative Radiotherapy Impairs the Stimulation of Breast Cancer Cell Proliferation and Invasion Caused by Surgical Wounding

Authors' Affiliations: ¹ Experimental Oncology 2, ² Breast Surgery Unit, ³ Radiation Oncology, ⁴ Pathology, ⁵ Medical Oncology C, and ⁶ Department of Breast Cancer Research, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy; ⁷ Department of Surgery and Molecular Oncology, University of Dundee, Scotland; and ⁸ Institute of Immunology, Witten/Herdecke University, Witten, Germany

Requests for reprints: Gustavo Baldassarre, Division of Experimental Oncology 2, Centro di Riferimento Oncologico National Cancer Institute, via Franco Gallini, 2, 33081 Aviano, Italy. Phone: 39-0434-659-759; Fax: 39-0434-659-428; E-mail: gbaldassarre{at}cro.it.

Purpose: After apparently successful excision of breast cancer, risk of local recurrence remains high mainly in the area surrounding the original tumor, indicating that wound healing processes may be implicated. The proportional reduction of this risk by radiotherapy does not depend on the extent of surgery, suggesting that radiotherapy, in addition to killing tumor cells, may influence the tumor microenvironment.

Experimental Design: We studied how normal and mammary carcinoma cell growth and motility are affected by surgical wound fluids (WF), collected over 24 h following breast-conserving surgery in 45 patients, 20 of whom had received additional TARGeted Intraoperative radioTherapy (TARGIT), immediately after the surgical excision. The proteomic profile of the WF and their effects on the activation of intracellular signal transduction pathways of breast cancer cells were also analyzed.

Results: WF stimulated proliferation, migration, and invasion of breast cancer cell lines. The stimulatory effect was almost completely abrogated when fluids from TARGIT-treated patients were used. These fluids displayed altered expression of several cytokines and failed to properly stimulate the activation of some intracellular signal transduction pathways, when compared with fluids harvested from untreated patients.

Conclusions: Delivery of TARGIT to the tumor bed alters the molecular composition and biological activity of surgical WF. This novel antitumoral effect could, at least partially, explain the very low recurrence rates found in a large pilot study using TARGIT. It also opens a novel avenue for identifying new molecular targets and testing novel therapeutic agents.